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The nature and extent of genetic discrimination among persons at risk for Huntington disease Bombard, Yvonne 2008

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TilE NATURE AND EXTENT OF GENETIC DISCRIMINATION AMONG PERSONSAT RISK FOR HUNTINGTON DISEASEbyYVONNE BOMBARDB.Sc., McGill University, 2002A THESIS SUBMITTED iN PARTIAL FULFILLMENT OFTHE REQUIREMENTS FOR THE DEGREE OFDOCTOR OF PHILOSOPHYinTHE FACULTY OF GRADUATE STUDIES(Interdisciplinary Studies)THE UNIVERSITY OF BRITISH COLUMBIA(Vancouver)May 2008© Yvonne Bombard, 2008AbstractHuntington disease (HD), the “Dancing Mania” of the Middle Ages, has alwaysbeen aparticular target of social stigma and discrimination. With the discovery of apolymorphic DNAmarker linked to HD in 1983, individuals at-risk for HD were ableto learn whether or not theyhad inherited the causative HD mutation and possibly escape its stigma and discrimination.Forthose who had inherited the HD mutation increased discrimination became a real possibility.Genetic discrimination (GD) refers to the differential treatment of asymptomaticindividuals or their family based on genetic differences. It has been over twentyyears since theintroduction of predictive testing (PT) for HD, yet little is known about the natureand extent ofGD and whether PT actually results in increased levels of GD. The objective of thisdissertationwas to use qualitative and quantitative methods to investigate the nature and extentof GDamong persons at-risk for HD.Qualitative findings provide insight into how individuals interpret, personalize andmanage GD. Results from the national survey indicate that 40% of respondents reportedatleast one experience of GD. Reported experiences occurred most often inreference to life anddisability insurance, and among family and friends. Surprisingly, there were fewreports of GD inemployment, health care and government settings. Experiences were not significantlyassociated with PT. However, the proportion of respondents who reported GD was 16%higheramong persons who have the HD mutation than among those that do not anduntestedrespondents. Interestingly, respondents’ family history (FH), ratherthan their PT result, was themajor reason given for their experiences as well as an important predictor of GD. Psychologicaldistress was a health outcome of GD.This is the first study to investigate the nature and extent of GD among an asymptomatictested and untested population. This dissertation provides evidence that GD is a frequentlyreported experience and a source of distress for persons at-risk for HD. These findings provideinsight for policy, identify areas where more education and support is needed,and providedirection to genetic professionals supporting their clients as they confront issues of GD.Table of ContentsABSTRACT.iiTABLE OF CONTENTSiiiLIST OF TABLESixLIST OF FIGURESxLIST OF ABBREVIATIONSxiACKNOWLEDGEMENTSxiiCO-AUTHORSHIP STATEMENTxivCHAPTER 1: INTRODUCTIONI1.1. STATEMENT OF PROBLEM 21.2. BACKGROUND21.2.1. HUNTINGTON DISEASE21.2.1.1. Introduction21.2.1.2. Epidemiology21.2.1.3. Clinicalfeatures31.2.1.3.1. Psychiatric features31.2.1.3.2. Cognitive features31.2.1.3.3. Movementfeatures 41.2.1.3.4. Early changes preceding HD onset41.2.1.4. Genetics51.2.1.4.1. Inheritance 51.2.1.4.2. CAG size and age of onset 51.2.2. PREDICTIVE TESTING FOR HUNTINGTON DISEASE61.2.2.1. Introduction61.2.2.2. Predictive Testing Programs for HD71.2.2.3. Uptake Rates of Predictive Testing 101.2.2.4. Psychosocial Impact of Predictive Testing for HD11III1.2.3. GENETIC DIscRIMINATIoN.131.2.3.1. Introduction131.2.3.2. Historical Perspectives141.2.3.3. Concept and Categories of Genetic Discrimination171.2.3.4. Examples of Genetic Discrimination181.2.3.5. Prevalence of Genetic Discrimination181.2.3.6. Fear of Genetic Discrimination201.2.3.7. Third Party Perspectives211.2.3.7.1. Insurance211.2.3.7.2. Employment 251.2.3.8. Ethical, Legal and Policy Considerations261.2.3.8.1. Ethical Issues 261.2.3.8.2. Legal Context281.2.3.8.3. Policy Considerations 311.2.3.9. Conclusion351.2.4. Gaps in Existing Research351.3. REFERENCES37CHAPTER 2: OVERVIEW OF RESEARCH PROJECT472.1 THEORETICAL PERSPECTIVE482.2 HYPOTHESIS AND OBJECTIVES 492.3 METHODOLOGICAL CHALLENGES502.4 RESEARCH DESIGN52Phase 1: Qualitative Study of the Nature of Concerns, Experiences and StrategiesforGenetic Discrimination53Phase 2: Questionnaire Development, Pretest and Pilot53Phase 3: Survey on the extent of genetic discrimination among personsat risk for HD 542.5 ETHICAL CONSIDERATIONS 542.6 REFERENCES56ivCHAPTER 3: THE NATURE OF GENETIC DISCRIMINATION 583.1 INTRODUCTION 593.2 METHODS 60Study Sample and Recruitment 60Data Collection 61Data Analysis 613.3 RESULTS 61Sample Characteristics 61Concerns and experiences of genetic discrimination 62Awareness events 63The Concept of Engagement with GD 64States of Engagement with GD 65The Process of Engagement with GD 66Forming meaningful interpretations of GD 66Personalizing the Risk for and Consequences of GD 69Factors influencing the degree of engagement with GD 713.4 DISCUSSION 723.5 REFERENCES 80CHAPTER 4: THE STRATEGIES USED TO MANAGE GENETIC DISCRIMINATION 834.1 INTRODUCTION 844.2 METHODS 86Recruitment and Participants 86Data Collection 86Data Analysis 874.3 RESULTS 88Participant Demographics 88Dimensions of the GD Strategies Model88‘Keeping Low” 89Minimizing GD 91VPreempting GD.93Confronting GD 954.4 Discussiori 974.5 REFERENCES 103CHAPTER 5: THE EXTENT OF GENETIC DISCRIMINATION 1075.1 INTRODUCTION 1085.2 METHODS 109Study Population 109Development of the survey instrument and testing 110Assessment of family history & genetic status 110Assessment of experiences of genetic discrimination 110Assessment of psychological distress 111Demographic information 111Administration of the survey 111Statistical analysis 1125.3 RESULTS 113Characteristics of the respondents 113Nature and extent of genetic discrimination 113Genetic status and genetic discrimination 115Reported reasons for genetic discrimination 116Predictors of genetic discrimination 117Psychological distress and genetic discrimination 1175.4 Discussiori 1185.5 REFERENCES 128CHAPTER 6: DISCUSSION 1316.1 INTRODUCTION 1326.2 SUMMARY OF FINDINGS 1336.3 INTEGRATING THE FINDINGS 1356.3.1 Genetic Discrimination: A multidimensional concept 135viGenetic distinctions or genetic discrimination9 135Subjectivity: An inherent component 1366.3.2. Experiences of Genetic Discrimination: The Nature and Extent 137Insurance Discrimination 137Discrimination in the Family 139Discrimination in Social Circles 143Employment Discrimination 143Government & Health Care Discrimination 1446.3.3. Family History: The fundamental issue 1456.3.4. Psychosocial Impact of Genetic Discrimination: Distress1476.4 PRACTICE RECOMMENDATIONS148Introduction148Predictors of Genetic Discrimination149Management of Genetic Discrimination150Avenues for recourse1526.5 POLICY RECOMMENDATIONS152Introduction152Public & Professional Awareness152Anti-Genetic Discrimination Legislation1536.6 FUTURE RESEARCH DIRECTIONS154Mechanisms of response to genetic discrimination154Concern for genetic discrimination: a major factor9154The multiple targets of genetic discrimination: what about thefamily members9 155New mutation families: An ideal comparison group155The full extent of genetic discrimination: considering frequency,duration & timing 1566.7 CONCLUSION1566.8 REFERENCES158VIIAPPENDIX .176Al. BEHAVIOURAL RESEARCH ETHICS APPROVAL 176A2. CONSENT FORMS 177A3. SEMI STRUCTURED INTERVIEW GUIDE 195A4. COGNITIVE INTERVIEW GUIDE 203A5. SURVEY INSTRUMENT 213VIIIList of TablesTABLE 1.1 WORLDWIDE PARTICIPATION RATES FOR PREDICTIVE TESTING FOR HD11TABLE 1.2 REGULATORY STRUCTURES CONCERNING GD ACROSS DEVELOPEDCOUNTRIES 34TABLE 3.1 SAMPLE DEMOGRAPHICS 77TABLE 3.2 PROPORTION OF CONCERN AND EXPERIENCES OF GENETIC DISCRIMINATION78TABLE 4.1 PARTICIPANTS’ DEMOGRAPHIC INFORMATION 102TABLE 5.1 DEMOGRAPHIC CHARACTERISTICS OF RESPONDENTS 124TABLE 5.2 EXPERIENCES OF GENETIC DISCRIMINATION125TABLE 5.3 PREVALENCE OF GENETIC DISCRIMINATION126TABLE 5.4 PREDICTORS OF GENETIC DISCRIMINATION127ixList of FiguresFIGURE 1.1 SUMMARY OF THE PREDICTIVE TESTING PROTOCOL FOR HUNTINGTON DISEASE 8FIGURE 1.2 SCHEMA REPRESENTING THE CONCEPT OF ADVERSE SELECTION USING HD AS AN EXAMPLE 24FIGURE 3.1 STATES OF ENGAGEMENT WiTH GENETIC DISCRIMINATION IN RELATION TO GENETIC STATUS AND RISKPERCEPTION FOR HUNTINGTON DISEASE 79FIGURE 4.1 STRATEGIES TO MANAGE GENETIC DISCRIMINATION (GD) 102xList of AbbreviationsCAG cytosine-adenine-guanine nucleotide repeatCl confidence intervalDNA deoxyribonucleic acidELSI ethical, legal and social issuesFH family historyGINA genetic information non-discrimination actGD genetic discriminationGTR genetic test resultHD Huntington diseaseHD+ persons with CAG expansionHD- persons without CAG expansionNT not tested: persons that have chosen not to test for the CAG expansionOR odds ratioPT predictive testingRNA ribonucleic acidSD standard deviationSDF socio-demographic factorsxiAcknowledgementsThis has been a very important journey for me and there are many people that I wouldlike to acknowledge for being part of it. Although this dissertation gives the impression of a solomission, it certainly would not have been accomplished without the support ofthe followingindividuals.First and foremost, I would like to thank my supervisor, Michael Hayden, whoseopenness and mentorship has been unwavering and a source of inspiration. Michael, thank youfor seeing the potential in me, helping me through the challenges and pushing me to reach mygoals. Your insight and support will last a lifetime.I would like to especially thank Joan Bottorff. Joan your guidance has been instrumentalto my success and has been one of the most gratifying aspects of this experience.The members of my supervisory committee — Jan Freidman, Susan Creighton, andGerry Veenstra - deserve special acknowledgement for their support and genuine enthusiasm ofmy project. Thank you for offering your time and expertise so generously. Your perseverancethrough our countless committee meetings is also much appreciated.I would like to express my sincere gratitude to the families who participated in this study;without their generosity this research would have not been possible. I am also grateful to themany people at the study sites who supported this work and believed in this project: JanePaulsen & Elizabeth Penziner, Mark Guttman & Christine Giambattista, Mark Ludman & JillMurphy, Patrick MacLeod & Jen Rice, Wayne Martin & Marguerite Wieler, Wendy Meschino &Clare Gibbons, Lynn Raymond & Joji Decolongon, Oksana Suchowersky & Mary Lou NicolsonKlimek, and Janet Williams.I am also very thankful to members of the Hayden laboratory. I especially thank LaurenCurrie, a talented and caring person whose assistance coordinating the survey administrationwas invaluable. Marcia MacDonald, Mahmoud Pouladi, Rona Graham, Simon Warby, AliciaSemaka, Jeff Carroll, Fiona Young, Meg Grant, Jeff Helm and others: thank you for lending yourears, letting me bounce my ideas and your genuine friendship over the years.I would also like to thank Sandra Taylor, Sue Treolar and Trudo Lemmens for stimulatingdiscussions and support with the methodological and legal aspects related to geneticdiscrimination. I am also indebted to Michael Hockertz and Jonathan Falkowski for theirtechnical assistance.I am deeply grateful for the financial support of the following organizations which hasallowed me to pursue this doctoral degree: Canadian Institutes for Health Research, MichaelSmith Foundation for Health Research, BC Medical Services Foundation, Child and FamilyResearch Institute.xl’Last but certainly not least, I would like to thank my husband Dean and my family —lrena, Michael, Hadar, Alisha and Daniel Bombard as wellas Michael, Marion, Jesse and SimonElterman - for their everlasting love and support. Even from a distance,they remained behindme every step of the way.XIIICo-authorship StatementChapter 3: The Nature of Genetic DiscriminationI conducted all of the interviews in this manuscript. I analyzed the data ofall the interviews,developed the theory, generated the tables and figures and wrote the manuscript.The initial concept for the study described in this and the following chapterswas conceived byMichael Hayden and myself and was subsequently developed in collaboration with ElizabethPenziner and Jane Paulsen. The interview guide was developed in collaboration with ElizabethPenziner and Jane Paulsen. Oksana Suchowersky and Mark Guttman helped recruit the studysample. Joan Bottorff revised the interview guide. Michael Hayden and Joan Bottorff advisedthe data analysis and writing of this manuscript.Chapter 4: The Strategies used to Manage Genetic DiscriminationThe design of this chapter was conceived by me. I collected and analyzed all the data. Igenerated the tables and figures and wrote the manuscript.The initial concept for the study described in this chapter was conceivedby Michael Hayden andmyself and was subsequently developed in collaboration with Elizabeth Penziner and JanePaulsen. Joji Decolongon, Mary-Lou Klimek, Oksana Suchowersky and Mark Guttman helpedrecruit the study sample. Susan Creighton provided practical advice regarding the managementof GD in the context of predictive testing for HD. Joan Bottorif revised the interview guide.Michael Hayden and Joan Bottorff advised the data analysis and writing of this manuscript.Chapter 5: The Extent of Genetic DiscriminationI designed the study including the survey instruments and survey administration, described inthis chapter with critical support of my supervisor, Michael Hayden. I adapted, pretest andpiloted the survey instrument. I performed all of the data analysis, generated the tables andwrote the manuscript.The initial concept for the study described in this chapter was conceivedby Michael Hayden andmyself and was subsequently developed in collaboration with Jane Paulsen. The members ofthe Canadian Respond-HD collaborative researchgroup*include the seven clinical sites whichhelped collect the survey data. Lauren Currie coordinated the data collection and data entry andassisted with some of the analysis. Michael Hayden, Joan Bottorif, Gerry Veenstra, JanxivFriedman and Susan Creighton provided intellectual inputon the survey instrument, providedmethodological advice, and advised the writing of this manuscript.*Canadian Respond-HD collaborative research group are:Mark Guttman & Christine Giambattista, Centre for Movement DisordersMark Ludman, Jill Murphy & Tina Babineau-Sturk, IWK HealthCentre.Patrick MacLeod & Jennifer Rice, Victoria General HospitalWayne Martin & Marguerite Wieler, University of AlbertaWendy Meschino & Clare Gibbons, North York GeneralHospitalLynn Raymond & Joji Decolongon, University of British ColumbiaOksana Suchowersky & Mary-Lou Klimek, University of CalgaryxvChapter 1: Introduction11.1. STATEMENT OF PROBLEMAlthough the inception of genetic testing for Huntington disease (HD) has led to muchresearch and clinical care devoted to its risks and benefits, the ethical, legal, and socialimplications of knowing one’s disease risk for HD are poorly understood. Genetic discrimination(GD), a potential risk of genetic testing, is the differential treatment of individuals or their familymembers based on genetic differences. It has been over 20 years since the globalimplementation of predictive testing for HD, yet considerable debate regarding the existenceand prevalence of GD continues. Although anecdotal reports of GD exist, empirical data areneeded to advance this debate and answer the fundamental ethical and social question: dopersons at risk for HD experience genetic discrimination? If so, does having predictive testinglead to increased levels of discrimination against individuals found to have the HD mutation?1.2. BACKGROUND1.2.1. HUNTINGTON DISEASE1.2.1.1. INTRODUCTIONHuntington disease (HD) is a debilitating inherited neuropsychiatric disease which wasfirst described in detail by George Huntington in his 1872 landmark paper entitled “On Chorea”(Huntington, 2003). The term chorea originates from choros, which means ‘dance’ in Greek,referring to its hallmark feature of rapid, involuntary dance-like movements. Huntingtondescribed individuals with HD as having “a dancing propensity.” In fact this classic feature of HDsubsequently led it to being branded as the “Dancing Mania” during the Middle Ages. In additionto chorea, individuals affected with HD suffer from mood and personality changes as well ascognitive impairment. HD symptoms usually become apparent between the ages of 35 and 45and then gradually progress until death from pneumonia, malnutrition, and/or heart failure occurapproximately 15 to 20 years after initial diagnosis (Harper, 1991; Hayden, 1981). Althoughclinical trials are now underway, no therapy is currently available to slow or prevent the disease.1.2.1.2. EPIDEMIOLOGYHD is a relatively rare disease with an overall prevalence of 1-10 per 100,000 (Hayden,1981). Its prevalence varies across ethnic groups and regions largely because of foundereffects. For example, immigrants carrying the mutant HD gene who settled over 100 years agoin Tasmania, Venezuela and Mauritius contributed to the high frequency of the diseasepresently seen in these areas (Hayden, 1981). Other countries such as Canada, Sweden,Scotland and England also have high frequencies of HD (Hayden, 1981). HD clusters mainly in2populations of European ancestry and is also noted to be relatively uncommonamongJapanese, African and American black persons (Hayden, 1981; Squitieri et al., 1994).1.2.1.3. CLINICAL FEATURESThe clinical features of HD include psychiatric, cognitive and movement disturbances.Itscharacteristics can be assessed using the Unified Huntington’s Disease Rating Scale(UHDRS).The UHDRS assesses four features of HD: motor function, cognition, behaviour,and functionalability (Kieburtz et al., 1996). While persons affected with HD usually present witha combinationof these features, the progression and severity vary from person to person and even,within thesame family. Although the presence of specific motor signs is the currentcriterion forestablishing a clinical diagnosis of HD, psychiatric and cognitive changes often precedetheonset of motor dysfunction (Diamond et al., 1992; Duff et al., 2007; Foroud et al., 1995; HahnBarma et al., 1998; Jason et al., 1988; Johnson et al., 2007; Kirkwood et al., 1999;Langbehnand Paulsen, 2007; Marshall et al., 2007; Morris, 1991; Snowdenet al., 2002; Solomon et al.,2007).1.2.1.3.1. PSYCHIATRIC FEATURESPsychiatric symptoms occur in 30-70% of persons with HD (Anderson and Marshall,2005). Personality changes often occur early in the disease. Family membersoften describethese changes as seemingly exacerbating existing personality traits of the person or,at times,may even seem to reverse a person’s character. For example, a previously irritable personmaybecome more irritable or a previously even-tempered individual may become aggressiveorhostile. Other psychiatric symptoms include irritability, aggression, depression, apathy,anxietyas well as obsessive thinking and compulsive behaviour (Anderson and Marshall, 2005; Burnset al., 1990; Paulsen et al., 2001). Delusions, paranoia, and psychosis have also beendescribed (Mendez, 1994; Paulsen et al., 2001). There is no predictable time whenthesepsychiatric changes begin (Anderson and Marshall, 2005; Morris, 1991), but they representsome of the most disturbing aspects of the disorder for caregivers, families and patients(Nordinetal., 1995).1.2.1.3.2. COGNITIVE FEATURESPsychiatric symptoms and cognitive decline are often linked as cognitive shortcomingsevoking anxiety and irritability in preclinical patients. Because of the insidious nature of thedisease, it is often difficult to distinguish early cognitive signs from everydaycognitive difficultiesthat people may exhibit as a result of being overworked, stressedor tired (e.g. forgetfulness,clumsiness or inability to concentrate). Visuo-spatial performance deficits may besome of theearliest cognitive changes in HD (Josiassen et al., 1983) and involve deficits in the abilitytocopy simple geometric or block designs and put together puzzles. The most prominent cognitiveimpairments involve executive functions, such as planning, organizing, sequencing,decision3making and judgment (Paulsen and Conybeare, 2005). Learning and memory deficits are mostfrequently reported and include slowed rates of learning and impaired recall (Massmanet al.,1990).One of the most prominent features of latter stages of the disease is the motor speechimpairment or dysarthia. Early speech impairments may include insufficient breath support andvarying prosody which progress to reduced phrase length and increased pauses (Podoll et al.,1988). Unlike psychiatric symptoms, patients often are aware of their initial cognitive decline andbecome frustrated and depressed as they realize they are unable to performat the level theywere able to previously. This period is associated with increased withdrawal from clinicalassessment (Paulsen and Conybeare, 2005) and suicide risk (Paulsen et al., 2005).1.2.1.3.3. MOVEMENT FEATURESThe movement disorder of HD includes chorea, the classic involuntary jerky movements,changes in saccadic eye movements, inability to suppress reflexive glances to novel visualstimuli, impaired rapid alternating movements, balance problems and restlessness (Siemers etal., 1996). Some patients do not notice these movement symptoms, but family members oftennotice them and report that the patient is fidgety and unable to sit still or concentrate on tasks(Paulsen JS and Conybeare, 2005). Chorea typically worsens in the middle stages of the illnessand then decreases as the person becomes more debilitated.1.2.1.3.4. EARLY CHANGES PRECEDING HD ONSETThere is strong evidence for the ability to detect cognitive and behavioural changesbefore the formal diagnosis of HD in individuals with the CAG expansion (the mutation in the HDgene responsible for the disease — see the following section for an explanation) (Diamond et al.,1992; Duff et al., 2007; Foroud et al., 1995; Hahn-Barma et al., 1998; Jason et al., 1988;Johnson et al., 2007; Kirkwood et al., 1999; Langbehn and Paulsen, 2007; Marshall et al., 2007;Morris, 1991; Snowden et al., 2002; Solomon et al., 2007). Subtle motor signs, neurologicaldeficits, psychiatric problems, neurophysiological alterations and brain changes often precedeonset of motor symptoms.Recent evidence has found motor timing variability increases in preclinical HD patientsas estimated onset of motor symptoms approaches (Hinton et al., 2007). Further researchindicates that verbal episodic memory declines in early pre-diagnostic HD patients and maydecline as striatal volume decreases and individuals approach the motor diagnostic threshold(Solomon et al., 2007). Subtle, pre-clinical psychiatric symptoms, including depression, anxiety,or obsessive-compulsiveness, are also present in pre-diagnosed individuals carrying the CAGexpansion (Duff et al., 2007).4With regards to neurophysiological changes, recognition of negative emotions,includinganger, disgust, fear and sadness, have been found to declineamong individuals with the CAGexpansion early in the disease process, and poorer performance is associatedwith closerproximity to clinical diagnosis (Johnson et al., 2007). Moreover, altered morphologyof cerebralcortex has been found in subjects with CAG expansionand no manifest disease. Specifically,enlarged gyral crowns and sulcal shapes suggest that abnormal neural developmentmay be anadditional component in the degenerative changes of HD (Nopoulos et al.,2007). Takentogether, these findings suggest that pre-clinical motor signs and neuropsychologicalperformance have prognostic importance in predicting diagnosisin HD and may assist withearly therapeutic interventions.1.2.1.4. GENETICS1.2.1.4.1. INHERITANCEHD is transmitted as an autosomal dominant trait (Hayden, 1981) affecting bothsexesand conferring a 50% risk of transmission to every child of a person withHD. HD is caused byan abnormal expansion of trinucleotide repeats at the 5’ of the huntingtingene. The mutantexpansion comprises an expansion of the cytosine-adenine-guanine(CAG) repeats in exon I ofthe HD gene (MacDonald et al., 1993).Typical of autosomal dominant diseases, HD results in a gain of toxic functionby themutant protein produced by the HD gene. Mechanisms including excitotoxiceffects ofglutamatergic transmission, mitochondrial dysfunction, transcriptional dysregulation,enhancedapoptosis or cell death, deranged vesicular trafficking, disordered proteolysis,and inflammationhave all been suggested as contributors underlying the neuronal dysfunction characteristicofHD (Hersch, 2003).As an autosomal dominant disorder, HD was noted to conform to the classic definitionofcomplete dominance (Wexler et al., 1987). That is, individuals with one (heterozygotes)or two(homozygotes) copies of the mutant allele present with similar severity ofsymptoms and shouldbe phenotypically (i.e. physically) indistinguishable. However, more recent evidence indicatesthat homozygous individuals present with an increased rate of disease progressionand a moresevere clinical course (Squitieri et al., 2003). These findings pointto a possible incompletedominance mechanism, which suggests that the mechanisms underlyingage at onset andprogression in Huntington disease may differ.1.2.1.4.2. CAG SIZE AND AGE OF ONSETThe HD gene is normally present in the human genome, since the gene is requiredfornormal cell functioning. The difference, however, betweena healthy person and one affected5with HD is the number of CAG repeats contained in the HDgene. Healthy individuals havebetween 9 and 26 CAG repeats, with most having 18 repeats on each allele. Individualsidentified with the HD mutation have a CAG repeat length over35 in one allele and areconsidered at ‘increased risk’ for developing HD in their lifetime, should they live long enough(Kremer et al., 1994). Some individuals with repeat lengths between 36-39 may never developsymptoms of HD in their lifetime, even if they live to an advanced age, as CAG expansionsbetween 36-39 are in the affected range, but are not fully penetrant (Langbehn et al., 2004;Rubinsztein et al., 1996). CAG repeat lengths between 27-35 are referredto as intermediatealleles. Individuals with intermediate alleles are not at risk of developing symptoms of HD butmay be at risk of having a child with an allele in the affected range. This occurs as a result ofspontaneous expansions of the unstable CAG repeats of intermediate alleles duringtransmission to the next generation. The risk of CAG expansion of intermediate alleles has beenobserved in cases when the parent transmitting the allele is male (Goldberget al., 1993).There is a significant inverse relationship between CAG repeat length and age of onsetof HD, with a larger CAG expansion associated with an earlier age of onset, given a person’scurrent age and clinical presentation (Langbehn et al., 2004). For example, current parametricsurvival models predict that a 40 year-old individual with 41 CAG repeats has a 95% chance ofdisease onset by the age of 60, while a 40 year-old individual with 44 CAG repeats is almostcertain to be affected by that age (Langbehn et al., 2004). However, caution must be exercisedwhen predicting age of onset for a particular CAG repeat length, as the precision of thepredictions is relatively low, with wide confidence limits. Predicting the age-range of diseaseonset in an individual based on CAG repeats is performed clinically. Furthermore, in addition toCAG length, other genetic and environmental factors are also likely to contribute to the variancein age of onset of HD (Rosenblatt et al., 2001).Genetic anticipation, characteristic of autosomal dominant trinucleotide repeat disorders,occurs in HD. Due to faulty DNA replication and other unknown mechanisms, the CAG repeatscan increase in number as the mutant allele is transmitted from generation to generation,particularly in the case of paternal inheritance. As a consequence, later generations tend tomanifest the disease at a younger age.1.2.2. PREDICTIVE TESTING FOR HUNTINGTON DISEASE1.2.2.1. INTRoDUCTIONThe discovery of polymorphic DNA markers associated with HD (Gusella et al., 1983;Wasmuth et al., 1988) led to the first predictive test for an adult onset genetic disease in 1986,6allowing at-risk individuals to learn with near complete certainty whetheror not they haveinherited the HD expansion (Fox et al., 1989; Haydenet al., 1987; Hayden et al., 1988). Initially,predictive testing was offered by linkage analysis, where polymorphic markersknown to behighly linked (or recombine infrequently) with HD were assessed usingblood samples collectedfrom family members from at least 3 generations (Haydenet al., 1988). This process requiredextensive participation among family members since consent and collectionof blood samplesfrom family members to establish segregation of genetic markers withthe disease locus wasnecessary to perform the linkage analysis. This requirement often precludedsome candidatesfrom testing because not enough relatives were availableor wished to cooperate, and somefamilies were genetically uninformative (Simpson and Harding, 1993).In addition, there wasalso the remote possibility of error if the HD gene and markers recombined.The discovery of a novel gene containing the CAG trinucleotide expansionthat isexpanded on HD chromosomes (MacDonald et al., 1993) heralded directand highly accurateanalysis of the CAG repeat, eliminating the necessity to request theparticipation and bloodsamples from relatives. While direct mutation analysis cleared the previous technicaldifficultiesassociated with linkage analysis, the psychosocial impact of learningthis information remainedlargely unchanged.Prior to the introduction of predictive testing, significant concerns were raisedaboutwhether it was ethical to offer predictive testing without the availabilityof a treatment to preventor interrupt progression of the disease (Craufurd and Harris,1986; Perry, 1981). There wasapprehension that disclosure of results may precipitate depression, breakdownof familyrelationships or suicide (Farrer, 1986).After substantial debate and consultation between scientists, families, andthe lay groupsthat represent patients and families with HD worldwide, predictive testing guidelinesfor HD wereestablished. These guidelines were developed in British Columbia (Benjaminet al., 1994) andsubsequently implemented worldwide, and have served asa model for predictive testing forother genetic and non-genetic conditions (Evers-Kiebooms et al., 2000; Hayden,2003).1.2.2.2. PREDICTIVE TESTING PROGRAMS FOR HDThe predictive testing protocols typically consists of a number of counselingsessionsthat deal with the risks and benefits of testing, psychosocial assessmentof available supportsystems and the potential for genetic discrimination, particularly in the areas ofinsurance andemployment (Brohoim et al., 1994; Went, 1990). The guidelines ensure thattest candidates areprovided with up-to-date information regarding HD, the testing proceduresand possibleconsequences, in order to make informed decisions and to ensure supportof healthy adaptationto their changed status.7Predictive testing is provided in the contextof a multidisciplinary health care teamincluding, where possible, geneticists, geneticcounselors, social workers, and psychologists.Eligibility criteria for predictive testinginclude: (1) a confirmed family history ofHD and an apriori risk of 50% or 25%, (2) ability toprovide informed consent, and (3) not havingbeen givena clinical diagnosis of HD (Benjaminet al., 1994). Candidates are encouraged tobring supportpersons to provide ongoing emotionalsupport during and after the testing process. Thefollowing outline provides a synopsis of the aims andtopics covered during each of the sessionswhich was originally developed in BritishColumbia, Canada for linkage analysis(Bloch et al.,1989; Fox et aL, 1989) and has been subsequentlymodified to reflect the provisions necessaryfor the direct test (Benjamin et al., 1994) (Figure 1.1).It should be also noted that this protocolcontinues to be used in Vancouver, Canada andmay not necessarily reflect the protocolfollowed by other genetics clinics providing predictivetesting for HD.Patient Callsor sReferredfor PTInformationPackage MailedTo Patient(3 weeks) (1 week)1(2weeksjIIFigure 1.1 Summary of the predictive testing protocolfor Huntington disease(adapted, with permission, from Benjamin et al.,1994)Session one provides candidates with informationabout the clinical description of HD,the genetics of HD, the direct analysis of CAG repeats and thebenefits and possible harms ofknowing one’s mutation status (Benjamin et al., 1994).At this time, candidates’ motives inpursuing testing and possible outcomes of the test are explored.Candidates are advised tosecure desired levels of insurance before proceeding withtesting and are made aware ofpossible implications of the results on futureinsurance assessments (Benjamin et al., 1994).The limitations of the test, available treatment options and current researchare also discussed.A medical and family history is taken documenting relevantaffected relatives and knownGAG sizes and current health statuses of siblings or other relatives.Particular emphasis is8placed on psychiatric episodes or history in the candidates, as adverse reactionsto test resultsare more prevalent among persons with a psychiatric history (Almqvist et al., 1999).Candidateswho raise concerns regarding psychological wellbeing before or after testing are referredforpsychological counseling (Benjamin et al., 1994), and testing may be postponed(although thisis a rare occurrence (Hayden, 2007)).The candidates are told that they may withdraw from the testing process atany time.Once the candidates are fully informed of the predictive testing process, geneticsof HD, andthat risks and benefits of testing, the candidates are asked if they still wishto continue withtesting and are asked to sign the consent form to have their blood drawn and proceedwith theprogram.A neurological exam, the final component of the first session, is performedto assessbaseline levels of chorea and other early signs of HD. Prior to the exam thecandidates areasked if they are aware or concerned about any signs or symptoms. Approximately5-10% ofpeople who enter predictive testing programs already manifest signs and symptomsof HD(Hayden and Bombard, 2005). The candidates are asked if they wouldlike to learn the results ofthe exam before the results of the exam are disclosed. This aspectis an important element ofthe psychological process of adjusting to a possible HD status as some individualsare notprepared to learn if they are presently showing clinical signs of HD whilefor others disclosure ofresults is part of a gradual process of adjusting to receiving an eventual clinical diagnosis(Blochet al., 1993). Careful assessment of these individuals and assessment of their psychologicalresponses to this information have allowed the development of approaches suitablefor theprovision of the diagnosis of HD to affected persons. If early signs are present,the candidatesare informed of them but it is stressed that soft signs may not necessarily be specificto HD,especially at an early stage. Before the session ends the candidates are asked if theywould likea letter sent to their family physician so that they can be informed of the candidates’ involvementin the predictive testing program. The decisions to learn of early neurologicalchanges andinform family physicians further demonstrate the importance the predictive testing programsplace on the personal autonomy of candidates.For candidates who live significant distances from the genetics centre, a rural protocol isin place where the remainder of the sessions are conducted by the family physician or anotherhealth professional in the community (chosen by the candidate). The genetics clinic mustsend aletter along with adequate materials on providing counselling and support following disclosure ofthe results (Benjamin et al., 1994).The candidates are notified that the results are not known to the genetics teamuntilshortly before the results session in order to provide counselling in an unbiased way (Benjamin9et al., 1994) and so that the candidates do not attempt to infer the results from the counsellor’sdiscussions during the next session(s). Moreover, previous experience indicates that 25%ofindividuals who enter the program choose not to learn the results (Quaid and Morris, 1993;Wiggins et al., 1992), thus the genetics team is not aware of the results until immediately beforethe candidates’ results session.The second session is intended to prepare candidates for the test results. Candidates’support persons or significant others are usually asked to attend these sessions in order toconduct the counselling jointly and assess levels of support. Discussions focus on what thecandidates expect of the results and how they will be assimilated into their lives. Counsellingalso focuses on whom in the family and candidates’ social circle is aware of their participation inthe program and their plans for disclosure. Candidates are advised that it may be best not tospecify the exact date they are receiving the results to these persons in order to circumvent anyundesired/untimely involvement following the results. It is also recommended that candidateshave a predetermined plan in place for the day they receive their results, regardless of theoutcome of the test.The candidates are asked again if they are still interested in proceeding with the test,given the lack of treatment to slow or stop progression of the disease (Benjamin et al., 1994). Ifthe candidate is still interested in proceeding, a date is set up for the results session a short timelater.The third session is usually a brief meeting where the results are presented to thecandidate in a clear, direct and unambiguous fashion (Benjamin et al., 1994). Despite efforts onbehalf of the team and candidate, shock usually ensues, and the candidates may be given timealone with the support person to digest the information.The fourth follow-up session occurs 2 weeks following the results for all persons and isdesigned to provide continuing support, contact or additional information (Benjamin et al., 1994).The timing of subsequent sessions is tailored to the results of the test as indicated bylongitudinal psychological studies (Almqvist et al., 2003; Wiggins et al., 1992). Follow up forpersons who were found to have the HD mutation occurs in person at intervals of 6 months toone year, while those who do not have the mutation are followed at similar intervals by phone orin person as needed. Ongoing contact at any time is always welcomed (Benjamin et al., 1994).1.2.2.3. UPTAKE RATES OF PREDICTIVE TESTINGAlthough previous assessments of families at-risk for HD indicated that predictive testingwas acceptable and should be made available (Craufurd et al., 1989; Decruyenaere et al., 1993;Evers-Kiebooms et al., 1987; Mastromauro et al., 1987; Meissen and Berchek, 1987), fewindividuals have requested this option as worldwide uptake currently ranges from 5% to 24%10(Creighton et al., 2003; Hayden, 1993). The geographical diversity of uptake rates both amongand within countries is notable (Table 1.1). The lowest uptake rates are currently in Austria andGermany, where participation is approximately 3-4% (Laccone et al., 1999), while uptake in theNetherlands has been reported as high as 24% (Maat-Kievit et al., 2000). In Canada, uptakerates range from 12.5% in the Maritimes to 20.7% in British Columbia, with an overall averageof 18% (Creighton et al., 2003). Issues of universal health care coverage, social programs andresearch activities may account for the differences in uptake among and within countries(Creighton et al., 2003).Country Testing Uptake Reported Prevalence Referenceof HDCanada 18% 8.4-23.3/1 00,000 (Shokeir, 1975)United Kingdom 18% 7.5/1 00,000 (Harperet al., 2000)the Netherlands 24% 6.5/1 00,000 (Maat-Kievit et al., 2000)France 5% 5/1 00,000 (Goizet et al., 2002)Worldwide study 5% 4/1 00,000 (The World Federation ofNeurology ResearchGroup on Huntington’sDisease, 1993)Germany, Austria, <3-4% 1-2.7/100,000 (Conneally, 1984;Switzerland Laccone at al., 1999)Table 1.1 Worldwide participation rates for predictive testing for HD(adapted, with permission, from Creighton et al., 2003)1.2.2.4. PSYCHOSOCIAL IMPACT OF PREDICTIVE TESTING FOR HDSince the inception of the HD predictive testing program, much research and clinicalcare has been devoted to determining the risks and benefits as well as the psychosocial effectsof predictive testing. The predominant reasons for requesting the predictive test have been torelieve uncertainty, inform reproductive decisions and plan for the future (Bloch et al., 1989).Reasons against testing often include the inability to cope with the results, lack of treatment,impact of the family and fear of genetic discrimination (Quaid and Morris, 1993). Studiesindicate that persons with and without the HD mutation (HD+ & HD-, respectively) significantlydiffer in terms of short-term (7-10 days), but not long-term (6-12 months), psychologicaladjustment to test results (Almqvist et al., 2003; Decruyenaere et al., 2003; Timman et al., 2004;Wiggins et al., 1992).11Initially, it was expected that predictive testing promised most benefit to those foundnotto have inherited the HD mutation (Kessler et al., 1987; Mastromauro et al., 1987; MeissenandBerchek, 1987). Although, in general, the majority of people who have received anHD- resulthad improved psychological function, a significant proportion (10%) have also neededadditionalsupport due to significant difficulty coping with their results (Huggins et al.,1992). Theseindividuals may be particularly vulnerable to adverse effects, which may be obviousif the testresult contradicts the individual’s consciously or unconsciously expected outcome or ifs/he hasmade irreversible decisions based on the belief that s/he would develop HD in thefuture. Theseadverse reactions largely occur between 2-12 months after testing (Huggins et al.,1992).Survivor’s guilt and development of new self-identities have also been describedamongHD- persons following testing (Tibben et al., 1990; Williams et al., 2000a). As a consequenceofthese phenomena, HD- persons may exhibit over-caring behaviour towardtheir HD+ andaffected relatives and may experience problems among their existing relationships. ForsomeHD- persons, restructuring their life perspectives may prove to be difficult.HD+ persons are considered to be at high risk for emotional difficulties in theshort-term.The highest level of distress occurs immediately after receiving test results (Almqvistet al.,2003). Within the first year, however, this is followed in most instances by adjustment and returnof distress and features of depression to baseline levels (Bloch et al., 1992). Numerousfactorsappear to facilitate adjustment to this information. The person’s patterns of communication andmode of dealing with significant stress in the past are crucial variables in this process.A priorhistory of psychiatric disorder is also a risk factor for difficult adjustment to results of predictivetesting (Bloch et al., 1992).Overall, there have been few long-term psychological consequences for HD testing(Bundey, 1997). Psychological distress is significantly reduced for both HD+ and HD- personsfollowing testing as compared to baseline levels prior to testing (Almqvist et al., 2003;Broadstock et al., 2000). Moreover, adverse events following testing are notably few. Thefrequency of clinically defined adverse events — namely clinical depression,psychiatrichospitalization, attempted suicide, a marked increase in alcohol consumption, planned suicide,or breakdown of a significant relationship with negative consequences - is 6.9% (14/202),andamong these the most frequent adverse event is diagnosed clinical depression (Almqvistet al.,2003). Furthermore, few catastrophic events such as suicide, suicide attempt or psychiatrichospitalization occur following predictive testing for HD. The worldwidefrequency ofcatastrophic events is 0.97% (44/4,527), a level similar to the general population (Almqvistetal., 1999). Lessons learned from long-term follow up studies point to the need to focus on test12candidates with low ego-strength and unspecified motivation for requesting testing, since thesecandidates exhibit most distress in the long-term (Decruyenaere et al., 2003).Taken together, knowing the results of the predictive test reduces uncertainty andprovides an opportunity for appropriate planning. The existence of few psychologicalconsequences point to the success of the detailed pre-test counseling that clearly excludesmany individuals with a greater likelihood of suffering an adverse event. Others argue thatpersons requesting predictive testing are a self-selected group, better equipped at handling‘bad’ news and typically have high ego strength and have more resources (Bloch et al., 1989;Codori et al., 1994). It is also possible that pre-test expectations of receiving a positive testresult may aid in mobilizing coping mechanisms such as denial (Tibben et al., 1993a). Aperson’s social context often shapes that individual’s perception of a test result. The perceptionof a test result as positive or negative is influenced by a person’s family dynamics, as testresults impact the family system as a whole (Kessler and Bloch, 1989; Williams et al., 2000b). Afinal explanation of why there have been few psychological consequences is that receivingpredictive test results, although undoubtedly an emotional experience, eventually just becomesone of many other events that impact individuals during the course of their lives.1.2.3. GENETIC DIscRIMINATIoN1.2.3.1. INTRODUCTIONSince the inception of predictive testing for HD, much research and clinical care hasbeen devoted to its psychological consequences. The ethical, legal, and social implications ofknowing one’s disease risk for HD, however, are poorly understood. A particular risk identifiedfrom the inception of the program is genetic discrimination (GD).GD refers to the differential treatment of individuals or their family members based ongenetic differences, as opposed to different physical features. GD has the potential to generateeconomic and social consequences, often beyond the individual to include their familymembers.While HD, the ‘Dancing Mania of the Middle Ages’ (Hayden, 1981), has always been aparticular target of social stigma and discrimination, GD is not limited to HD. As history dictates,subtle influences of economic pressures along with health policies intended to improve thehealth of society can spiral quickly into eugenic practices across many diseases andpopulations. Today, with the increasing transparency of the human genome and reliance onemployers and private insurance companies to access health care, threats of genetic abuse areever more real. It stands to reason that third parties have a direct interest in genetic information13and there is potential for misuse of that information to discriminate against healthyindividuals onthe basis of genetic predisposition for a disease.Indeed the fear of GD exists and is widespread (Apseet al., 2004; Hall et al., 2005).Fear of GD has prevented individuals from undergoinggenetic testing (Apse et al., 2004;Peterson et al., 2002) and participating in genetic research (Hadley et aL, 2003). Theseeffectshave significant public health implications, as GD directly hinders individuals’potentiallybeneficial engagement with genetic medicine and achievementof important scientific andmedical advances. For example, many women at increased risk for breastcancer as well aspersons at risk for HD do not undergo genetic testing in fear of its social implicationsforthemselves and their families (Armstrong et al., 2003; HaIl and Rich, 2000; Quaidand Morris,1993). Furthermore, those who do volunteer for genetic research studies may be a self-selectedgroup who may not represent the most generalizable findings.1.2.3.2. HISTORICAL PERSPECTIVESConcern about genetic discrimination has historical support. The dawn of the20thcentury saw some of the most racist currents sweep through Western society. Againstthebackdrop of a perceived rise in social problems, such as unemployment, criminality,prostitutionand alcoholism, anxiety developed among the North American middle classabout anincreasingly defective social system. With the rediscovery of Mendel’s laws of inheritanceandbelief that such social issues are a consequence of defective geneticcharacteristics, came thebirth of eugenics (Garver and Garver, 1991).Eugenics, stemming from the Greek word, eugenes, literally meaning well-born’, refersto the science intended to improve the human race by influencing hereditary factors (GarverandGarver, 1991). Negative eugenics and positive eugenics refer to the systematicefforts tominimize the transmission of deleterious genes and maximize the transmission of desirablegenes, respectively (Garver and Garver, 1991).The interest and promise of eugenics was supported by biologists and physicians whofuelled existent prejudicial views that immigrants from Southern andEastern European, and ofAsian or Jewish decent were responsible for the social problems as well as the eventual dilutionof the ‘Anglo-Saxon stock’ (Garver and Garver, 1991). In Germany, the plightof racial hygienein a post-World War I depression climate created the basis of their well-known negativeeugenics programs. Systematically, this respective propaganda laid the groundwork forrestrictive immigration laws as well as involuntary eugenic sterilization lawsin the US, Canadaand Germany. These laws mandated compulsory sterilization of institutionalized individualswhowere ‘feebleminded’, criminals, orphans, ‘mentally retarded’, epileptic or generally ‘diseasedordegenerate’ persons (Garver and Garver, 1991).14Germany took it one step further with euthanasia programs aimed, initially, at theannihilation of children born with birth defects, mental retardation and genetic disease.Soonafter, these programs expanded to the mass murder of healthy children who were Jewishor ofother undesirable races (Garver and Garver, 1991). By the 1940’s their program developedintothe widespread extermination of the Jews, Roma people, mental patients, and war prisoners.HD did not escape these eugenic programs. In fact Charles Davenport, one of the earlyleaders of the eugenics movement and founder of the Eugenics Records Office inCold SpringHarbor, New York, used HD as the prototype from which to justify restrictive immigrationreforms. From surveys he conducted on the extent and origin of HD in NewEngland, heconcluded:All these evils in our study trace back to some half-dozen individuals includingthreebrothers, who migrated to this country [from England] during the17thcentury. Had thesehalf-dozen individuals been kept out of this country much of misery might havebeensaved (Davenport and Muncey, 1916).Given that the introduction of HD could not have been stopped, Davenport turnedto the nextbest option: legislation to prevent its spread, as he indicated:It would be a work of far-seeing philanthropy to sterilize all those in whichchronicchorea has already developed and to secure that such of their offspringas showprematurely its symptoms shall not reproduce. It is for the state to investigateeverycase of Huntington’s chorea that appears and to concern itself with all the progeny ofsuch. That is the least the state can do to fulfill its duty to the as yet unborn. A state thatknows who are its choreics and knows that half of the children of every one suchwill (on the average) become choreic and does not do the obvious thing to preventthe spread of this dire inheritable disease is impotent, stupid and blind and invitesdisaster. We think of personal liberty and forget the rights and liberties of the unborn ofwhom that state is the sole protector. Unfortunate the nation when the state declinestofulfill this duty’ (Davenport and Muncey, 1916).Such ideas represented the undertones of the immigration policies of North America andwere later echoed during the eugenic policies in Nazi Germany. With its psychiatric andhereditary nature, HD was an obvious candidate for inclusion in the compulsory sterilizationlaws in Germany (Harper, 1992).Germany and North America were not the only countries where compulsory sterilizationstook place, of HD at risk persons in particular. Spillane and Philips, U.K. scientists studying HDfamilies in Wales, also supported the need for such legislation. As they indicated:Perhaps with the repeated advice and education, some would voluntarily abstain frommarriage but the majority would no doubt be prepared to accept the even chance thatnature offers them. We are thus left with the conclusion that only legislative measure willeventually succeed in eradicating the disease (Spillane and Phillips, 1937).15Approximately 3,000 affected HD patients were involuntarily sterilized beginningin 1933(Harper, 1992). Genetic Health Courts were establishedin Germany and mandated to reviewand administer sterilizations and exterminations of psychiatric patients. Theseconditions weredocumented, along with the medical abuse used to justify these procedures,in the followingaccount:The sterilization laws show how professional powers and state authority reinforcedoneanother. Nine ‘diseases’ were selected: hereditary feeble-mindedness, Schizophrenia,manic-depression, hereditary epilepsy, Huntington’s chorea, hereditaryblindness,hereditary deafness, hereditary malformations, and (including the historical rootsof thelaw) severe alcoholism. A system of hereditary courts was established; eachtribunalwas composed of a lawyer, a medical officer and a doctor with specialist trainingin racialhygiene. The medical officer could initiate proceedingsas well as adjudicate, anddoctors were in the majority. The state established primacy of reproduction, but lefttheoperating of the controls to the medical profession (Weindling, 1989).Details gleaned from extensive studies on HD and expert testimoniesled to theidentification (and quite possible extermination) of HD patients, asymptomaticrelatives andchildren who were of reproductive age (Harper, 1992). For example, Panse, a neurologistwhoundertook a systematic survey and analysis of HD in Germany, acknowledgedhis role inidentifying HD families to the Genetic Health Courts:We proceeded in a manner that we reported all choreic cases, and moreoverallsuspicious cases and finally not yet choreic sibs and offspringas being at risk tothe health authorities.... 79 cases located and diagnosed by us were reportedto thehealth administration. They have been passed on to the Genetic Health procedure,ifthey were of an age to procreate (Panse, 1942).HD epitomized the prejudice towards a perceived existence of genetic perfection.Tensions ensue between the state and individuals when cost-effective or utilitarianhealthpolicies are used to trump individual rights and privacy. Lessons learned from thepast, whileillustrative of the potential abuses of genetics, may also be an important foreshadow.DuringNazi Germany and the eugenic period of North America, presymptomatic personscould not beidentified. Today they can. In today’s climate of accurate, commercially-availablegenetic testsand the increasing dependence on private institutions for health care and accessto socialgoods, the threat of eugenics and genetic discrimination may come in much more subtle formsof exclusion of social goods, such as insurance, employment and potentially alsosocial rightssuch as education, adoption and health services. Without careful foresight and protections inplace, individuals with HD and other disorders may again be subject to geneticabuse anddiscrimination. Lessons learned from the past must be kept in the foreground of discussionsonthe use of genetic information today, if only to remind us of the fine line between use andabuse.161.2.3.3. CONCEPT AND CATEGORIES OF GENETIC DISCRIMINATIONOne of the earliest expressions of concern about the potential for this type ofdiscrimination was by Kenen and Schmidt who published a paper in 1978 warning of thedangers of stigmatisation of individuals genetically identified with the sickle cell trait.Subsequently, Paul Billings and colleagues in 1992 published some of the first case studiesregarding negative treatment of people in the US allegedly because of their geneticcharacteristics. In this paper, Billings et al first used the now-familiar concept of “theasymptomatic ill” and warned of the potential emergence of a “genetic underclass” (Billings etal., 1992).Genetic discrimination (GD) was first described by Billings et al (1992) as the differentialtreatment of individuals or their relatives due to actual or presumed genetic differences asopposed to discrimination based upon phenotype. Billings et al (1992) classified victims of GDunder one of three categories. The asymptomatic ill is a category used to describe individualswho are healthy yet are found to have a hereditary disorder through genetic testing. Victims whofall under this category have early or adult onset disorders that have been properly managed, orare found to be heterozygote carriers or presymptomatic carriers (e.g. HD+ persons). Althoughthey are clinically healthy, persons in this group are treated as if they are chronically ill byvarious societal institutions (Billings et al., 1992).A second class comprises (a)symptomatic individuals who have a clinical diagnosis (e.g.Hemochromatosis) and are discriminated against because of an inaccurate or incompleteunderstanding of the clinical variability underlying many genetic disorders (i.e. penetrance,variable expressivity, and genetic heterogeneity). In these instances decisions were basedprimarily on a diagnostic label, assuming that the diagnosis equates to the most severe form ofthe disorder, without regard to the severity of the condition for each individual (Billings et al.,1992).The final category is the at-risk group: individuals who are currently healthy but are atrisk for a genetic disease and are undecided about whether to undergo testing. In thiscircumstance discrimination becomes a double edged sword: discrimination may ensue as aresult of forgoing testing as well as testing and discovering they have the causative gene. Beingat risk for HD was an example in this category, where Billings et al (1992) found that adoptionagencies, for example, rejected families who were at 50% risk for HD. While these situationswere the first to present this important ethical and social dilemma, a few highly publicized caseshave since come to light.171.2.3.4. EXAMPLES OF GENETIC DISCRIMINATIONExamples of genetic discrimination (GD) in the public domain are few. Casesthat havebeen documented have been largely anecdotal or based on limited casereports. However,there have been a few high profile reports.Some of the most prominent cases of GD arose inthe early I 970s where many AfricanAmericans were denied insurance, jobs and educational opportunitiesbecause they werecarriers of sickle cell anemia, even though they were quite healthy (Kenenand Schmidt, 1978;Rennie, 1994). Another well-publicized report involved the BurlingtonNorthern Santa FeRailway (BNSFR) which secretly tested its employeesfor a chromosomal deletion of a protein(peripheral myelin protein-22 on chromosome 17), which was thoughtto predispose to asyndrome similar to carpel tunnel syndrome (Schulte, 2004). The employeeswere never madeaware of the purpose or motivation of the test and were concurrentlyseeking disabilitycompensation as a result of carpal tunnel syndrome that occurred on thejob. BNSFR intendedto deny disability benefits to employees found to have the mutation associated with carpeltunnel syndrome, arguing that the mutation, not the job, was thecause (Gottlieb, 2001).Another alleged report involved treatment of a symptomatic individual.Upon learning ofher Alpha-I -antitrypsin deficiency, a woman underwent preventative replacement therapy,which was covered by her employer’s health insurance. Shortly after beginningher treatment,she was fired from her work despite the fact that she was healthyand received excellentperformance reviews (Miller, 1998).In relation to HD there was the recent report of a healthy German teacher was deniedajob because she had a family history of HD (Burgermeister, 2003). During routinemedicalexamination that all applicants to the German civil service, including teachers,have to undergo,this teacher was refused a permanent position because of theperceived future risk ofabsenteeism and medical costs (Burgermeister, 2003). Under German law medical authoritiescan reject applications for civil service jobs on the basis of ill health. Thisteacher subsequentlywent to court to win the right to refuse to take predictive testing (Burgermeister,2003).These cases, although somewhat anecdotal, exposed an importantethical and socialissue. However, the prevalence of genetic discrimination is unknown.1.2.3.5. PREVALENCE OF GENETiC DISCRIMINATIONAttempts to document the extent of GD have been limited to cohorts of symptomaticindividuals or third hand reports (Apse et al., 2004; Kasset al., 2007; Lapham et aI., 1996; Lowetal., 1998).18The first empirical study on GD from the perspectivesof genetic support group memberswas reported by Lapham et al (1996) in which 332 membersfrom a representative 101 diseasegroups were surveyed by telephone. They found thatas a result of a genetic disorder (i.e.symptoms), 25% of respondents or affected familymembers believed they were refused lifeinsurance; 22% believed they were refused health insurance;and 13% believed that they weredenied or let go from a job (Lapham et al., 1996). Whilethis was the first study to examine theextent of GD, the sample consisted of symptomatic individuals,third hand reports and waslimited to insurance and employment settings.Low et al (1998) compared experiences of GD betweena sample of individuals with agenetic condition (genetic sample) and a representative sampleof the general population andfound that the genetic sample experienced significantlymore GD (33.4% vs 5%, p0.0l) (Lowet al., 1998). They also found that 13% of respondents who represent no adverseactuarial andgenetic risk (non-carriers, carriers of autosomal recessivediseases) experienced problems withinsurance that respondents believed to be a result of their family history. Theseresults aresignificant since they show that those with genetic diseases in their families areat significantlyhigher risk for GD. Finally, their results point to the tendencyof insurers to misinterpret andmisuse genetic information in their actuarial assessments.Although Low et al (1998) assembleda representative sample, it consisted of symptomatic respondents. In factthey purposefullyexcluded surveys of unaffected carriers from their analysis. The questionas to whether theywere assessing GD as opposed to disability discrimination is an importantlimitation.The work of Apse et al (2004) was the first study to report perceptionsof GD among anasymptomatic sample. Among their sample of individuals at risk for colorectal cancer(CRC), 7%reported GD experiences in the way of premium increases, denial of lifeand health insurance,difficulty in obtaining coverage, and perceived inabilityto change jobs (Apse et al., 2004).However, upon further analysis, the reported experiences of GDwere not related to CRC but toother genetic and non-genetic conditions. Important limitations of thisstudy were that theirfindings included third hand reports which were ultimately unrelated to their risk forCRC andwere restricted to the insurance setting.Kass et al (2007) published the first study to compare GD experiencesamong geneticand non-genetic conditions, namely, cystic fibrosis, sickle cell disease, breast/ovariancancer,colon cancer, diabetes and HIV/AIDS. A total of 27% of theirsample reported being deniedinsurance or offered it at a prohibitive rate’ (Kass et aI., 2007). They also foundthat those withgenetic conditions are 2-3 times more likely to report GD when obtaininginsurance. It isunknown how representative their sample was becausea response rate was not provided.19Furthermore, their sample consisted of “persons with chronic medical conditions”,used third-hand reports and was also limited to the insurance setting.In the context of HD specifically, a US case study analysis documented experiencesofGD in 44% of a subset of HD respondents (Geller et al., 1996). In theirsurvey of 27,790individuals and children at risk for genetic disorders discovered276 reports of GD among the623 HD respondents (Geller et al., 1996). Of the 206 follow-up verification interviewsconductedfive cases concerned discrimination against individuals at-risk for HD. These reportsincluded:life insurance rejection, coercion by a physician to undergoprenatal genetic testing and abort anaffected fetus, two cases of adoption denials and a job refusal forthe US Air Force (Geller et aL,1996).Related discussion on GD in the HD literature involves GD being cited as an importantreason for declining predictive testing despite the fact that test-related expenseswere coveredby some states for Americans (Quaid and Morris, 1993). Many persons at-risk for HDbelievedthat the financial risk of potentially losing health insurance wastoo high to outweigh the benefitsof learning of one’s genetic status (Quaid and Morris, 1993). Moreover,health careprofessionals’ concerns focused on the possibility that individuals would feela fiduciaryresponsibility to disclose results to their employers. Professionals wereconcerned thatindividuals would also feel pressure to terminate affected pregnancies. Furtherthey believed apotential exists for the misuse of genetic information to stigmatize those found tohave the HDmutation (Craufurd and Harris, 1986; Harper, 1993).1.2.3.6. FEAR OF GENETIC DISCRIMINATIONThere is substantial public apprehension Concerning the uses of genetic information.A2003 public opinion telephone survey found that a large majority of Canadians (1092/1200;91%) reject the right of insurance companies to ask for genetic information, evenif applicantsare aware of a genetic condition (Government of Canada, 2003). This survey also revealedthat90% (1080/1 200) of individuals opposed the notion that employers should have access to the GIof workers or job applicants (Government of Canada, 2003). In fact anothersurvey found that18% of surveyed Americans (18/100) did not reveal genetic informationto insurers and another17% (1 7/1 00) did not reveal any information to their employers (Laphamet al 1996) in fear ofGD. These results imply a high level of distrust among Canadians and Americans with regardtotheir genetic privacy and use of their genetic information.A large scale study of insurance concerns among a US and Canadian hemochromatosispopulation found that 40% of individuals in their 86,859 sample were concernedthat genetictesting may lead to difficulty in obtaining or keeping ‘insurance’ (it was not stated whichtype ofinsurance) (Hall et al., 2005).20Health insurance discrimination is a major threat for womenin seeking breast cancer riskassessment. Over half (48/78, 61.5%) of eligible U.S. women decline testingfor the BRCAI/2susceptibility gene for fear of health insurance discrimination (Peterson et al., 2002).Moreover,concern about health insurance discrimination was foundto be inversely associated with thedecision to undergo testing. Statistically speaking, approximately half of thosewho declinedwould be positive (Peterson et al., 2002) and, therefore,deny themselves possiblepsychological relief, preventative management and/or treatment opportunitiesdue to fear of GD.In the context of HD specifically, the threat of health insurance discriminationhasimpelled some at-risk Americans to seek predictivetesting in Canada (Hayden, 2007). Stillothers, Canadian and American, have sought predictivetesting under the auspices of anonymityin fear of insurance discrimination for themselves and their families (Burgesset al., 1997).These types of situation creates difficulties for cliniciansand candidates seeking anonymoustesting as the quality of patient care, such as appropriate counselingand follow up, iscompromised in an anonymous provision.A comparative case study analysis of U.S. genetic counselors and geneticists alsorevealed interesting insights into their perceptions of GD. Almost all (27/29, 92%)geneticcounselors have found that adult patients seeking predictive testing approachgenetic testingwith some awareness and concern for health insurance discrimination (Hall andRich, 2000).Although the majority of genetic counselors noted that they believed the actualincidence ofdiscrimination to be very low, a significant majority (20/29, 67%) found patientsto be veryconcerned about GD. According to these counselors, 38% (11/29) of adultsrequestingpredictive testing eventually decline due to health insurance discrimination concerns(Hall andRich, 2000). Interestingly, according to these counselors, individuals seekingpredictive testingfor HD demonstrate an acute knowledge and concern for genetic discrimination(Hall and Rich,2000). In fact, it has been suggested that concern among these patients may comefrom theirown experiences with affected family members.1.2.3.7. THIRD PARTY PERSPECTIVES1.2.3.7.1. INSURANCEInsurance is a business contract which transfers the risk of a loss from an individualto agroup of individuals who are sharing the loss on some equitable basis(Ostrer et al., 1993).Since insurance institutions provide a commercial product, not a socialgood, the questionbecomes one of access which can be understood only through a comprehensiveanalysis of theinsurance system.There are many types of insurance, all of which protect against a specific form ofloss.Life insurance, for example, provides income security to beneficiaries in the eventof the21insured’s death (Knoppers and Joly, 2004). Disability insurance offers financial security when anaccident or illness causes a disability, no longer allowing the insured to work. Critical illnessinsurance, on the other hand, provides a lump-sum payment in the event the insured becomesseriously ill with a specified illness. Finally, mortgage insurance protectsa lender or investoragainst loss if the borrower is unable to repay the mortgage. Similarly, mortgage life insurancepays off the mortgage if the borrower dies.Unlike Canada, where health insurance is covered by its universal health care system,private health care insurers are the major sponsors of health care services inthe U.S. There arevarious types of health insurance carriers where the cost of insurance and eligibility depends oncategories of insurance carriers. Commercial, generally for-profit companies provide benefits toindividuals and groups and reimburse the insured directly for medical expenses (Jecker, 1993).Health care service contractors (HCSC5), such as Blue Cross- Blue Shield, hold exclusivecontracts with a network of health care providers and reimburse a provider or hospital. HealthManagement Organizations (HMOs) typically undertake a contractual agreement whichprovides health services directly to the insured, with hospitals and physicians incorporated in theHMO.By its very nature, insurance is discriminating. The process of medical underwriting,classifying risk, discriminates between applicants by pooling them into at-risk groups (Knoppersand Joly, 2004). Premiums, for life insurance as an example, are based upon the risk of dying inthe near future and they are calculated using information such as sex, age, health status,lifestyle and medical history of the applicant and her family. If the insurer accepts the applicant’srisks, the insured is then assigned to a group of insured people with similar risk factors andcharged the appropriate premiums. In this way the ‘discrimination’ is as actuarially sound aspossible — that is, based on rational, scientifically sound and empirically supported assessments(Anderlik and Rothstein, 2001).Based on the principle of “utmost good faith,” applicants have a legal obligation todisclose any relevant information at the time of application so that a contract can be entered intoon an “equal information” basis (Canadian Life and Health Insurance Association, 2000). Thus,applicants are required to disclose family history and relevant test results. Companies oftenrequire a physician’s statement of the applicant’s current physical condition as well as all testresults. Further, when individuals carrying a disease associated gene attempt to renew orupgrade policies, insurers may impose additional restrictions. Likewise, tests that predict the riskof having children with genetic diseases also could provide a basis for denying coverage forfuture dependents.22Within the insurance system there are various types of insurance. Individualinsurancedetermines an individual’s eligibility using medical underwriting,with each insurer prescribing itsown range of acceptable risk factors. In contrast, groupplans do not require individualapplicants to complete a medical form. Group plans involvea contract between an employerand the insurer. Many group plans are based on the costs of previous claims fromthe group(Jecker 1993). Therefore, individuals with medical liabilitiesincrease group costs and raisecosts to their employers.In essence, the premise of insurance is that the lucky subsidize thecost of loss for theunlucky. By reducing the uncertainty about individuals’ future health status,genetic testing mayweaken the principle of risk-spreading and mutuality of information upon whichinsurance isfounded. Individuals who discover a decreased risk for a diseasemay be able to target their fewareas of risk and purchase insurance accordingly, or they may drop out of the insurancemarketaltogether. Conversely, individuals aware they are ata higher risk of early death from a genetictest purchase more life insurance at bargain prices. This is the basis underlyingadverseselection, a phenomenon that the insurance industry has used to rationalize the useof geneticinformation for insurance underwriting.Adverse selection refers to the asymmetrical process by which people make decisionsbased on information known to them but not revealed to the insurer. Over time,insurers willexperience a higher overall rate of death, which will raise premiums for all buyersto cover thehigher costs, which may then lead individuals at low risk to buy less life insuranceand may evendrive some with the lowest risk entirely out of the market and further increase theprice of lifeinsurance (Armstrong et al 2003) (Figure 1 .2). This, insurers argue, will eventuallylead to thecollapse of the insurance market, since the original risk sharing model willshift to a risk poolmade up of primarily those with high risk.23GeneticTestingFigure 1.2 Schema representing the conceptof adverse selection using HD as an example(adapted, with permission, from Armstrong et al., 2003, ofWiley-Liss, Inc. a subsidiary of John Wiley&Sons, mc)The risk of adverse selection may be exaggeratedsince only a relatively small numberof diseases are caused by single genesand ultimately large claims will affect adverseselections. Evidently women testing positivefor the BRCA1 mutation do not capitalizeon theinformation asymmetry by buying disproportionatelylarge amounts of insurance (Zick etal.,2000). Furthermore, the predictive valueof most genetic tests is currently limited,even in thecase of HD with regards to low penetrant alleles (CAGrange: 36-39). Still, a positive test resultdoes not necessarily mean that a personwill develop a disease. Likewise, thereare manyfactors, environmental or social, that affect thesusceptibility of disease manifestation. Further,apositive test result may motivate a person to takespecific steps to significantly alter thelikelihood of developing the disease. Then again, anegative test result may instilla false senseof security that may reduce precautionary measuresthat may lead to another disease orpremature death. Moreover, as treatments become available forgenetic diseases, the risk ofbeing affected by a genetic disease will declineand fears of adverse selection shouldfade.Ultimately the heart of the debate centres onthe role of insurance in our society.Ifinsurance remains considered a commercial contract,and not a social good that is of significantsocial importance and that should therefore be sharedand accessible to all membersof a givensociety, then current practice using GI to set premiumsmight be permissible as long as theinformation is scientifically and actuarially valid andconfidentiality is respected. But, if insurancePurchaseless insurance/I24is deemed essential and necessary (especially given the current climate requiringlife insuranceto access other social goods and thus full participation in social life) theninsurance moves tothe status of a societal right, based on concepts of social solidarity, and is subjectto laws andconventions governing equal access and discrimination (Lemmens,2000).Insurance and employment are inherently linked, as the vast majority of individualsobtain their life or (extended) health insurance policies throughtheir employers’ (or spouses’employers’) group plans. While concerns of GD relate to both insurance and employment,asillustrated below, the use of genetic information in employment presents its own issues.1.2.3.7.2. EMPLOYMENTIn the employment landscape, workers fear that employers will use their confidentialgenetic information to their disadvantage. Presumably, employers may be ableto lower theirinsurance and sick leave costs by weeding out individualsat increased risk for a medicalconditionIndeed a small proportion of employers admitted to pursuing this option. A 1989surveyof 400 employers affiliated with Northwest Life Insurance found that 15%of employers plan tocheck the genetic status of prospective employees and their dependents beforemaking joboffers (Geller et al., 1996). In fact 15% of 332 individuals at risk for a genetic conditionhad beenasked questions about genetic diseases on a job application (Laphamet al., 1996).Unsurprisingly, the vast majority (87%) of those respondents declared that they wouldnot wanttheir employers to know if they were tested and found to be at high risk for a geneticdisorder(Lapham et al., 1996). These feelings are echoed in the general population,as surveys foundthat 92% of 1,211 Americans sampled oppose allowing employers access to theirgeneticinformation (Hudson et al., 2004). Importantly, concern about employers’access to geneticinformation, is growing, since this figure is up from 85% in 2002 (Hudson et al., 2004).Indeed individuals with medical liabilities increase group insurance costs and thereforeraise costs to their employers. Thus, the costs of including high risk or ill individualsmay proveprohibitive. Employers wishing to limit health care costs may exclude high riskindividuals byrefusing to hire them or promote them, by firing them, or by eliminating or reducingtheirinsurance benefits. Further, when individuals carrying a disease associatedgene attempt torenew or upgrade policies, employers may impose additional restrictions.While employers are legally restricted from making pre-employment medical inquiries,there are limited legal restrictions (in the US and Canada) prohibitingemployers from requestingmedical information, including genetic information, after a conditional offer of employmentbyway of pie-placement medical exams, which may include physical exams and bloodtests aswell as a general medical release of an individual’s medical records (Rothenberg etal., 1997).25Further, an employer may request annual medical exams from whichrecent genetic testinformation may be gleaned.It is important, however, to distinguish between the use of genetic information to screenpotential or current employees for the purposes of reducing human resource costs andmaximizing profits from genetic monitoring. Genetic monitoring involves periodic testing ofemployees to identify potential effects of long-term exposure to workplace toxins (Office ofTechnology Assessment, 1990). Thus employers woulduse such information to protect oraccommodate occupational health and safety of their employees with known conditions or risksaffected by particular work environments. It is also possible that employers could use thisinformation to their employees’ detriment to deny jobs or worker’s compensation claims, or toshirk their responsibility to adhere to safe and healthy workplacestandards by selectingemployees free of genetic susceptibilities to environmental hazards (Schulte,2004).The use of genetic information in the workplace presents societal risks that may havesignificant impact on employment possibilities, health insurance, health management andprivacy. Being intertwined as they are, employment and insurance settings are the biggestthreats for GD. Thus, policy-makers need to develop legislation or regulatory policy to addressthese concerns.1.2.3.8. ETHICAL, LEGAL AND POLICY CoNsIDETIoNs1.2.3.8.1. ETHICAL ISSUESBeauchamp and Childress’s (2001) classic principles of bioethics - autonomy, justiceand beneficence — may be used to demonstrate that genetic discrimination is morallyunacceptable and unethical (Beauchamp and Childress, 2001).Respect for autonomy entitles people to be fully informed and free agents, and to berespected in and of themselves. More generally, it refers to the right to independence or self-determination and privacy (Beauchamp and Childress, 2001). Privacy encompasses manydifferent rights, including the right to limit access to a person, the right to be left alone and theright to confidentiality (Rothstein and Anderlik, 2001). GD infringes on autonomy, privacy and inturn confidentiality when a third party requests an individual to take a genetic test as a conditionto receive goods such as a job or insurance. If that person would have otherwise chosen not toknow that information, they lose the freedom to remain ignorant of their genetic risk, and theylose control over access to their bodies as well as their genetic information,which in turn maybe disseminated beyond their control (RothStein and Anderlik, 2001). Hence, when knowledgeis forced upon a person, choice and the ability to be an autonomous agent are removed.It may be argued that harm is inflicted to that person if they did not wantto learn of theinformation or were otherwise not prepared for it, potentially producing psychological, emotional26or familial harms. Furthermore, it can not be assumed that it is always better to know a geneticrisk, given the variability in treatment or management options and, especially, when little may bedone where an incurable genetic disease is concerned. Moreover, knowing about one’s geneticmakeup can cause an uneven playing field for other members in the family, which may lead toaltered family dynamics. A related dilemma occurs when the informed individual disclosesgenetic information to an uninformed relative that results in the infringement of a familymember’s personal autonomy. By learning of one’s genetic information and disclosing thisinformation to other family members, the informed person impinges on his or her familymembers’ ability to be autonomous agents, should they have preferred to remain in ignorance.The principle of justice requires that ‘like cases be treated alike’ (Beauchamp andChildress, 2001). This principle is the core ethical principle enshrined in the United NationsEducational, Scientific and Cultural Organization’s (UNESCO) 1997 Universal Declaration onthe Human Genome and Human Rights which states in Article 6:no one shall be subjected to discrimination based on genetic characteristics that isintended to infringe or has the effect of infringing on human rights, fundamentalfreedoms and human dignity (UNESCO, 1997).Many other national constitutions and declarations of human rights worldwide havesimilarly acknowledged that “each individual is entitled to lead a life in which geneticcharacteristics are not the basis for unjust discrimination” (Council of Europe, 1997; HumanGenetics Commission, 2002).A related principle, genetic equity, posits that since humans are born equal, they areentitled to freedom from discrimination and equality of opportunity to flourish, and geneticinformation, like race, gender or otherwise, should not be used to limit that equality (Harris andSulston, 2004).The principle of justice may be directly applied to actuarial fairness in insuranceassessments. It is important, however, to distinguish between rational and irrationaldiscrimination. In insurance, irrational discrimination results from decision making on the basisof faulty or incomplete data, or from misunderstandings of genetic science or of the implicationsof genetic test results for morbidity and mortality (Anderlik and Rothstein 2001). Unfortunately,there is no way to monitor irrational discriminatory acts, even though there are laws that prohibitthe unjustified use of unsound actuarial data for risk calculations in many countries, includingCanada (Canadian Life and Health Insurance Association, 2000).Rational insurance discrimination refers to scientifically sound and empirically supporteduse of genetic information for assessments. Thus it is permitted to base risk calculations onsuch characteristics as age, individual and family history, health status, occupation, serum27cholesterol, and alcohol and tobacco use (Rothstein and Anderlik, 2001).Ironically, moreinformation available to insurers is better since the more precisethe discriminations, the greaterthe actuarial fairness of the system. Essentially, discrimination on the basisof geneticcharacteristics is rational unless it can be demonstrated that it is not unfair. Thus theburden ofproof is on those who discriminate to prove the fairness in doingso (Harris and Sulston, 2004).GD in reference to the principle of beneficence, theduty to do good (i.e. charity, kindacts or otherwise virtuous behaviours), requires consideration of the consequencesof generalsocial practices. The consequences of allowing insurers and employersto use geneticinformation in their assessments propagates the existent climate of fear whichhas impelledindividuals to avoid testing (Apse et al., 2004; Hall et al., 2005) and not take advantageofpossible interventions which could lead lower morbidity and mortality associated withgeneticconditions (Rothstein and Anderlik, 2001). From the Utilitarian perspective, whichpromotes thegreatest good for the greatest number, fear of GD limits individuals’ participationin research(Hadley et al., 2003) which may have significant impact on the achievementsof medicaladvancements, impacting society as a whole.GD expresses an underlying notion of genetic determinism, in which genes fullydetermine our fate (Hellman, 2003). Moreover, the practices of making employmentandinsurance decisions on the basis of genetic traits, therefore, convey the notionthat someindividuals are intrinsically flawed and by extension, are less suitable (Hellman, 2003). Bothofthese notions are morally troubling as this view implies a limited contribution of personidentity,individuality, free will, equality, and the ability to control one’s destiny.Genetic discrimination, albeit in the subtlest forms, seems highly reminiscent of theeugenic crusade towards genetic perfection. Although these genetic determinist ideals arebecoming increasingly untenable now that research is revealing complex interactionsamonggenes and environment in the development of human traits (even in the pathology of HD(Rosenblatt et al., 2001; van Dellen et al., 2005)), promoting legislation againstgeneticdiscrimination would express change in our current practices as well as what is morallypermissible.1.2.3.8.2. LEGAL CONTEXTA specific federal law does not exist in Canada which prohibits GD. The CanadianCharter of Rights and Freedoms and Human Rights Act prohibit discrimination on thebasis ofrace, national or ethnic origin, colour, religion, sex, age or mental or physicaldisability(Government of Canada: Canadian Heritage, 2007). Provincial human rights codes also existthat protect against discrimination in employment on the grounds of sex, race, color, ethnicity,28marital status and disability (Ontario human rights commission, 1999). Clearly,geneticinformation (GI) is not included.More recently, the Supreme Court of Canada has found that the term “handicap”in theQuebec Charter of Human Rights and Freedoms includes the perception of a handicapand theactual or perceived possibility that an individual may develop a handicap in the future(Quebecv.Boisbriand, 2000). In fact this interpretation now appliesto the definition of “disability” in mostprovincial human rights codes. Ontario, for example, adoptsa ‘socio-political dimension’ ofdisability where “disability must be interpreted to include its subjective component,sincediscrimination may be based as much on perceptions, mythsand stereotypes, as on theexistence of actual functional limitations” (Ontario human rights commission, 1999).This allowssome measure of protection for genetic predisposition as well as the perceivedpredisposition inthe employment environment (although one would likelybe subject to increased scrutiny) butthe protection offered by human rights codes in the insurance context is far moredifficult todiscern.Insurers are bound by privacy laws which protect the personal informationof individualsbut differ in scope. The Privacy Act protects federal government employees’personalinformation. In the private sector, the Personal Information Protection and Electronic DocumentsAct (PIPEDA) regulates how private organizations may collect, use or disclosepersonalinformation of customers or employees during federal and provincial commercialtransactions(Privacy Commissioner of Canada, 2003). It is importantto note that neither acts’ definitions ofpersonal information make specific mention of genetic information, genetictesting or geneticservice.Most provinces have established laws that overlap substantially with PIPEDA. CurrentlyQuebec is the only province that has privacy legislation for both private and public institutions,which includes genetic information; however, insurance companies are not prohibitedfromcollecting and using medical information with the appropriate informed consent.In summary, the Privacy Act regulates the collection, use and disclosure ofpersonalinformation held only by federal government agencies. PIPEDA extends protectionto personalinformation used in commercial activity related to federal works, undertakingsor businesses.Moreover, while the definition of personal health information likely includes genetic informationand the current interpretation of what constitutes disability has been expanded, it remainsto beseen if current protection and case law is sufficient or whether specific protection forGI iswarranted.The legal landscape surrounding GD in the U.S. is quite different. Americansarecovered by three federal discrimination laws. First, the Rehabilitation Act prohibitsemployment29discrimination on the basis of handicap by federal agencies.Aside from being restricted tofederal agencies, this Act does not apply to persons with a genetic predisposition.Second, the Americans with Disabilities Act (ADA) prohibits an employerfromdiscriminating against an individual because of a protected disability. Although the ADAextendsto both private and public agencies, the ADA applies only to persons who aresymptomatic anddoes not cover insurance underwriting policies (Natowicz et al., 1992).Finally, the Health Insurance Portability and Accountability Act of 1996 (HIPAA) providessome protection against GD in the U.S., such as prohibiting theuse of genetic information indenying or limiting health insurance coverage for members of a group plan (Rothenberget al.,1997). It also maintains that genetic information should not be regardedas a preexistingcondition in the absence of a formal diagnosis (Rothenberget al., 1997). Further, it bans grouphealth plans from disclosing health information to employers, and requires consentfor any otherdisclosures. However, the law does not provide protection for persons seeking insurancein theindividual market, nor does it provide privacy protection. HIPAA also does not prohibitratingbased on genetic information or prevent health insurers from disclosing or demandingaccess togenetic information. Moreover, it does not prohibit employers who may request thatemployeestake genetic tests and disclose that information (Shinaman et al., 2003).There are 36 states in the U.S. that have enacted laws regulatinguse and access ofgenetic information in health insurance and 32 states that prohibit employmentdiscriminationbased on genetic information (National Conference of State Legislatures, 2007).State laws arenot uniform and only afford individuals limited rights against discrimination. Therefore,the majorproblem with the majority of the individual state legislation is that the state laws are narrowinscope and have limited penalties for violation. This leaves many loopholes anda patchwork ofsafeguards.Recent U.S. initiatives have seen the introduction of the federal Bill entitled GeneticInformation Nondiscrimination Act (GINA) to address the spotty nature of the currentstate laws.GINA aims to prohibit the use of GI in health insurance and employment decisions ata nationallevel. Specifically, GINA will prohibit group and individual health insurers fromusing a person’sGI in determining eligibility and setting premiums as well as requesting or requiringpotentialapplicants undergo genetic testing. Furthermore GINA would bar employers from usinggenetictest results in their hiring, firing, job placement, or promotion decisions (Hudson, 2007). The billdefines GI as information about the genetic tests of an individual or familymember, or theoccurrence of a disease or disorder in family members of an individual. A genetictest refers tothe analysis of human DNA, RNA, chromosomes, proteins, or metabolitesthat detectsgenotypes, mutations, or chromosomal changes (Bettinger, 2007). While the billoutlines that30civil action may be pursued in response to a violation of the prohibitions outlined, the exactpenalties are not stated.On January 16, 2007 the Genetic Information Nondiscrimination Act of 2007 wasintroduced by Hon. Louise M. Slaughter as House resolution H.R. 493. Following a seriesofreferrals and reports, GINA has passed in the U.S. House of Representatives, by a vote of 420-3 on April 25, 2007 (National Human Genome Research Institute, 2007). As of the writing of thisdissertation, GINA is currently awaiting the Senate’s review.Given the uncertainties and gaps in state and federal protection in the US and thecomplete lack of legal safeguards in Canada, comprehensive federal legislation to establishminimum protections is needed to ensure that advances in genetic technology and researchmay be realized with minimal social discrimination.1.2.3.8.3. POLICY CONSIDERATIONSMany bills have been developed in the US, yet few have been successful. The reasonunderlying this obstacle in the development of comprehensive legislation is that a cleardistinction between genetic and non-genetic information is difficult to achieve. Various lawshave defined genetic information differently. Genetic information can be restricted to informationabout the actual genetic material itself, such as DNA or RNA, or proteins. In some laws thedefinition of genetic information extends to include family history. To complicate matters further,some have argued that most medical tests are ordered in an effort to detect conditions orpotential conditions that have an underlying genetic contribution (Lemmens, 2000).Another ambiguity underlies multifactorial diseases where genetic and non-genetic testsmay be performed to detect a susceptibility to disease. Consider a situation where anasymptomatic individual is identified with a genetic susceptibility to colon cancer via a genetictest. That individual would be theoretically protected by a genetic anti-discrimination law.However, another individual may have a non-genetic test that identifiesa precancerouscondition that may at some point in time lead to cancer. Both these individuals may be at risk fordeveloping the same disease, yet the second individual would not be protected by the same lawby virtue of the fact that her test was non-genetic (Beckwith and Alper, 1998). Thus, currentlaws are flawed because they are either too broad or too narrow in their definition of GI(Lemmens, 2000).Another problem that afflicts policy making is the inherent overlap between genetic andother health information, thus making it not feasible to separate genetic information from otherhealth information in a person’s medical file. Given that family history information and otherrelated information is often combined in a person’s medical file, attempts at separating geneticfrom other medical information in patient records would be burdensome, impractical and may in31fact compromise the quality of patient care (Rothstein and Anderlik, 2001). Ultimately it may bedifficult to classify diseases and risk factors into genetic and non-genetic categories as manydiseases comprise both categories or will not neatly fit into one category or the other (Murray,1997).The final complication considers the consequences of bestowing genetic informationspecial safeguards. Is genetic information inherently special, or deserving of special treatment?Some argue that special treatment increases the perceived stigma attached to geneticdiseases, since singling out genetic information may indicate that genetic diseases may indeedbe particularly shameful (Rothstein and Anderlik, 2001). Information held in a person’s medicalfile, such as demographics, financial, social and behavioural data may provide many personaldetails. However, proponents of bestowing genetic information special treatment argue thatgenetic information is more sensitive than other medical information. Genetic information is alsoregarded as unique because of its predictive nature and social, psychological and economicimplications. Moreover, there is a greater chance of misinterpretation given the advancedtechnology and variability in the validity of genetic tests. Finally, and most importantly, geneticinformation is highly identifiable and reveals information about family members, and thus haswide impact beyond just the individual (Hodge, Jr., 2004).Legislative prohibition is often regarded as the most radical and inflexible approach. Apopular alternative is the adoption of a wait and see approach or moratorium. A moratorium is atemporary and voluntary agreement on behalf of the insurers (frequently achieved with thesupport of the government) to abstain from asking and using genetic tests in their premiumassessments. Moratoria are attractive to insurers since they are flexible, temporaryarrangements which may be tailored as appropriate. Moratoria are an ideal measure inresponse to public pressure to technological developments where governments or regulatorsare unsure about a suitable regulatory structure (Lemmens et al., 2004) and allow time forresearch to take place or allow the insurance industry to formulate an alternative policy strategy.A limitation of such an approach is the voluntary nature of the arrangement which relies on thegoodwill of those involved (Lemmens et al., 2004).Moratoria range in scope from partial to unlimited. Under partial moratoria, insurerswould not request that an applicant undergo testing, but may request the results of previoustests (Lemmens et al., 2004). Under limited amount moratoria, insurers would not ask anapplicant to undergo genetic testing or request previous test results for policies under a certaindollar amount. Beyond this ‘threshold or ceiling’, insurers would be permitted to request and usethe genetic testing in their premium assessments. Such a system exists in the U.K. whereinsurers do not request or use genetic information for life insurance policies below £500,000 and32disability insurance or critical illness insurance policies below £300,000 (Secretaryof State forHealth, 2003). Companies are permitted to use the results of genetic tests thathave beenapproved by the Human Genetics Committee in the U.K., an advisory bodydesigned to reviewthe actuarial and scientific validity of genetic test information.To date, the genetic test for HD isthe only test currently approved (Secretary of State for Health, 2003). On theother end of thespectrum, an unlimited amount moratorium would envisage a situation where insurerswouldnever ask potential applications to undergo testing or use results from previous tests(Lemmenset al., 2004). Limited or partial moratoria are currently in effect in the U.K., Canada,Greece,New Zealand, South Africa, Switzerland and Turkey. Moratoria have recentlyexpired in thefollowing countries: Australia, Finland, France, Germany, Ireland and Sweden (Lemmenset al.,2004). (Table 1.2)33000CD<0Z3DQ-CD“DTØCD(DO0gg)g)3(I)-‘D.-‘c_Q_<ci_1•0.-I CD - CDCD-I. 0 0 C, -I. 0 C, 0 C, CD -‘ =CDC) C, B 0 0 0. CD CD 0 CD C, 0 = -I. -I CD 0IOØG)nmtocDcDOou>DD=D5CCDCt)(I)CDNDQ)CD0D3-®E3•DCDQ.3Q)5o_35.CD ?.>CD0. --oDiL3-‘ a•CxXXXXXXXXJXX.2-.2-2-.-.0)0)CD0)0)Cl)0.0.——0.——xxXX--X><XX><XXXXXXXXXXXXX-X-XXXXXX-.><C.)Some countries have established a system of regulatory review of theuse ofgenetic tests. In such a system the government appoints an expert panel which reviewsthe actuarial reliability, validity and social impact of using certaingenetic tests proposedby insurers to set premiums (Lemmens et al., 2004). Such isthe case in the U.K. inconcordance with their recently extended moratoria, wherethe only test approved foruse is the HD predictive test (Secretary of State for Health, 2003). Ontario hassupportedsuch a system in their recent recommendations (Lemmens et al., 2004).1.2.3.9. CONCLUSIONClearly, developing policies to address the concerns and experiences ofGD iscomplex. The definition of genetic information, what constitutesGD and what the publicperceptions and fears all need to be understood in order to inform policy developmentand address this issue comprehensively. While HD has servedas a model for thedevelopment of predictive testing guidelines and a leader on research and clinical careof the psychological consequences of testing, the social consequences,however, havereceived little attention. Given the lack of empirical research on GDin general, and withrespect to HD in particular, this dissertation studied the nature and extent of GD inorderto answer these fundamental ethical and social questions towardsthe ultimate goal ofprotecting individuals from unfair discrimination over thingsof which they have nocontrol.1.2.4. GAPS IN EXISTING RESEARCHWhile extant literature is replete with theoretical discourse and anecdotalevidence regarding GD, the perspectives of those at-risk or who have experiencedGD —the targets of discrimination - have been excluded. A descriptionof the concerns andexperiences of those facing these issues has surprisingly been overlooked.Moreover,the insurance and employment settings have received a disproportionate amountofattention with regards to GD. Understandably these settings are the focus of existingdiscourse on GD since they may be more tangible to determine. Yet the relationshipsamong family members and friends following testing or knowledgeof genetic risk are ofequal, if not of more importance, especially in the field of genetics, and havebeenneglected thus far. 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Neuropsychol. 24, 133-145.Solomon,A.C., Stout,J.C., Johnson,S.A., Langbehn,D.R., Aylward, E.H., Brandt,J., Ross,C.A.,Beglinger, L., Hayden,M.R., Kieburtz,K., Kayson, E., Julian-Baros,E., Duff,K., Guttman,M.,Nance,M., Oakes,D., Shoulson,l., Penziner,E., and Paulsen,J.S. (2007). Verbal episodic memorydeclines prior to diagnosis in Huntington’s disease. Neuropsychologia 45, 1767-1776.Spillane,J. and Phillips,R. (1937). Huntington’s Chorea in South Wales. Quarterly Journal ofMedicine 6, 403-423.Squitieri, F., Andrew,S.E., Goldberg,Y. P., Kremer,B., Spence,N., Zeisler,J., Nichol, K.,Theilmann,J., Greenberg,J., Goto,J., and (1994). DNA haplotype analysis of Huntington diseasereveals clues to the origins and mechanisms of CAG expansion and reasons for geographicvariations of prevalence. Hum. Mol. Genet3, 2103-2114.Squitieri,F., Gellera,C., Cannella,M., Mariotti,C., Cislaghi,G., Rubinsztein, D.C., Almqvist,E.W.,Turner,D., Bachoud-Levi,A.C., Simpson,S.A., Delatycki,M., Maglione,V., Hayden,M.R., andDonato,S.D. (2003). Homozygosity for CAG mutation in Huntington disease is associated with amore severe clinical course. Brain 126, 946-955.45The World Federation of Neurology Research Group on Huntington’s Disease (1993).Presymptomatic Testing for Huntingtons-Disease - A World Wide Survey. Journal of MedicalGenetics 30, 1020-1 022.Tibben,A., Duivenvoorden,H.J., Vegtervandervlis,M., Niermeijer,M.F., Frets,P.G.,Vandekamp,J.P., Roos,R.A.C., Rooijmans,H.G.M., and Verhage,F. (1993). Presymptomatic DnaTesting for Huntington Disease - Identifying the Need for Psychological Intervention. AmericanJournal of Medical Genetics 48, 137-144.Tibben,A., Vegter-van derVlis,M., Roos,R., van de Kamp,J.J., Frets,P.G., and Verhage,F. 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Ethical Issues Policy Statement on Huntingtons-Disease Molecular-GeneticsPredictive Test. Journal of Medical Genetics 27, 34-38.Wexler,N.S., Young,A. B., Tanzi,R. E., Travers,H., Starosta-Rubinstein,S., Penney,J.B.,Snodgrass,S.R., Shoulson,l., Gomez,F., RamosArroyo,M.A., and. (1987). Homozygotes forHuntington’s disease. Nature 326, 194-197.Wiggins,S., Whyte,P., Huggins,M., Adam,S., Theilmann,J., Bloch,M., Sheps,S.B.,Schechter,M.T., and Hayden,M.R. (1992). The Psychological Consequences of PredictiveTesting for Huntingtons Disease. New England Journal of Medicine 327, 140 1-1405.Williams,J.K., Schutte,D.L., Evers,C., and Holkup,P.A. (2000a). Redefinition: coping with normalresults from predictive gene testing for neurodegenerative disorders. Res. Nurs. Health 23, 260-269.Williams,J.K., Schutte,D.L., Holkup,P.A., Evers,C., and Muilenburg,A. (2000b). Psychosocialimpact of predictive testing for Huntington disease on support persons. American Journal ofMedical Genetics 96, 353-359.Zick,C.D., Smith,K.R., Mayer,R.N., and Botkin,J.R. (2000). Genetic testing, adverse selection,and the demand for life insurance. Am J Med Genet 93, 29-39.46Chapter 2: Overview of Research Project1A version of this chapter will be submitted for publication as:Yvonne Bombard, Gerry Veenstra, Joan L. Bottorff and Michael R. Hayden. On stigma: new insights from anempirical study on genetic discrimination among persons at risk for Huntington disease.472.1 THEORETICAL PERSPECTIVEThe theoretical framework informing this research study is based upon Goffman’sStigma Theory (1963). Scholars define stigma as a distinguishing attribute that discreditsor devalues a stigmatized person’s identity within a particular context (Crocker et al.,1998; Goffman, 1963; Jones et al., 1987). Stigma results in labeling, negativestereotyping, exclusion, discrimination and low status in the context of a power situation(Link and Phelan, 2001). Stigma is a broad Concept under which prejudice anddiscrimination are inextricably linked: stigma permeates many stereotypes, which arecollectively held beliefs about members of a social group. Prejudice is the endorsementof negative stereotypes, and discrimination is the behavioural response based onprejudice (Arboleda-Florez, 2003).Goffman distinguishes three types: tribal identities, abominations of the body,and blemishes of individual character (Goffman, 1963). Tribal identities refer to the socialsituation into which one is born. This may include: religious, ethnic, racial or nationalgroups. Abominations of the body represent physical ailments, such as: deformities,illnesses, and paralysis. Goffman uses blemishes of individual character, such as drugaddictions, to describe moral transgressions of weakness of will. Furthermore, Goffmancharacterizes various dimensions in his definition of stigma. Such dimensions include:concealibility, stability, disruptiveness and the extent to which a stigma is physicallyunappealing to others (Goffman, 1963).Stigmatizing ‘marks’ or diseases are further distinguished by their visibility andobtrusiveness. Goffman describes those with disorders that are stigmatizing and thatcan not be hidden or disguised as discredited, while describing those with the conditionsthat allow people to “pass as normal” as discreditable. Whereas the discredited may dealwith problems of “impression management”, the discreditable may face difficulties of“information management” (Goffman, 1963).An interesting distinction is drawn by Scambler and Hopkins in their Hidden-Distress model, which distinguishes between enacted and felt stigma. Enacted stigmarefers to actual discrimination, whereas felt stigma refers to the fear of suchdiscrimination (Scambler and Hopkins, 1986). Their model, as applied to epileptic adults,asserts that on diagnosis, adults experience felt stigma before exposure to enactedstigma. Furthermore, as a result of felt stigma, people adopt strategies of non-disclosureand concealment of their symptoms (i.e. seizures) and their diagnostic label. Their modelclaims that cases of enacted stigma are relatively few, and as a function of successful48concealment, felt stigma typically proves more disruptive than enacted stigma (Scamblerand Hopkins, 1986).Stigma is a powerful social phenomenon with widespread effects on its targets.Stigma leads to potential prejudice and discrimination across a broad range of socialcontexts. Stigmatized individuals are discriminated against in the housing market,workplace, educational settings, health care, and the criminal justice system (Major andO’Brien, 2005; Sidanius J and Pratto F, 1999). Discrimination directlyaffects the socialstatus, psychological well-being, and physical health of the stigmatized (Allison K.W.,1998). Stigma can be a source of stress for stigmatized individuals that poses someunique demands on the individual (Miller and Major, 2000). To cope with these stressorsindividuals rely on physiological, cognitive, emotional and behavioural resources.In applying this conceptual framework to the proposed study, persons at risk forHD can be considered to possess a form of tribal identity, as the nature of their geneticstatus is a matter of inheritance. They are also discreditable because they are notdisplaying overt symptoms of HD and, therefore, face issues of information managementand likely use various cognitive, emotional and behaviour strategies to manage GD. It isthe intent of this study to ascertain whether and to what extent these individuals sufferfrom felt or enacted stigma and to determine how they cope with or manage GD.2.2 HYPOTHESIS AND OBJECTIVESThe availability of predictive testing for HD by linkage analysis in 1986 heralded thefirst predictive test for an adult-onset disorder. Subsequent to this a direct test predictingonset of HD was made available in 1993. By determining the number of CAG repeats inthe HD gene, this test can “predict” whether an individual will develop HD in her lifetime.Genetic testing has allowed at-risk individuals to relieve their uncertainties and plan forthe future; however, there are many unexplored issues surrounding the implications ofthis process.A longstanding question since the inception of HD predictive testing is: doesparticipating in predictive testing lead to increased levels of discrimination againstpersons who are found to have the HD mutation? Moreover, on a fundamental level,does GD exist in persons at risk for HD and, if so, to what extent and in whichsituations? A full characterization of the prevalence of GD and the situations in whichpeople encounter discrimination are required to obtain full appreciation of the socialimpact of learning of one’s genetic status for HD.49Given the anecdotal evidence of the existence of GD in other populations andcountries, it is hypothesized that:1. GD is experienced by persons at risk for HD in Canada.2. Persons at-risk for HD who participate in predictive testing report morediscriminatory experiences compared to those who choose not to participate inpredictive testing.3. HD mutation carriers encounter more discrimination compared to HD non-carriers or individuals who chose not to undergo testing.Accordingly, the overall purpose of this study is to investigate the nature andextent of GD. The specific research objectives were:1. To describe the nature of experiences, concerns and strategies for GD fromthe perspective of the HD community.2. To examine whether genetic testing is associated with increased levels ofGD.3. To examine whether mutation carriers (HD+) are more likely to experienceGD vs. non-carriers (HD-) or those who did not test (NT).4. To identify the prevalence of experiences of GD in insurance, employment,government, health care, family, and social settings.5. To define and differentiate between the relationships of GD based on familyhistory and genetic testing.6. To examine the socio-demographic predictors and health outcomes of GD.2.3 METHODOLOGICAL CHALLENGESCurrent evidence of GD has been considerably hampered by variousmethodological constraints ranging from definitional issues, sampling issues, toresponse issues (Treloar et al., 2004). The definition of GD has varied from narrow tobroad definitions referring, for example, to the misuse of genetic information by insurersor, more broadly, to the use of genetic information for the psychosocial disadvantage ofindividuals as a result of prejudice or stigma (Treloar et al., 2004). Given its legal nature,50GD can also be conceptualized as the unjust distinctions, which may be prohibited tovarying degrees depending on the legislation available in a particular jurisdiction. From ahuman rights perspective, GD may also refer to socially unacceptable distinctions,whereas an actuarial view would classify GD as irrational distinctions (Rothstein andAnderlik, 2001).Ultimately the generally recognized concept of GD refers to differential treatmentof asymptomatic individuals or their family members based on real or perceived geneticcharacteristics, which involve elements of social unacceptability as well as irrationality.Given the subjective nature of this social phenomenon, it is best to allow those at risk orthose who have experienced GD to define and identify the conceptual dimensions andcharacteristics of GD themselves.It is important to acknowledge that the process of making distinctions or providingdifferential treatment may not necessarily only involve disadvantage. Individuals may betreated differentially but in a positive way. This may be especially true in the case of HDsince genetic information is inextricably linked to family, and outcomes such asincreased understanding and support may also occur after disclosure of geneticinformation.Targeting the appropriate subpopulations in which to investigate GD alsopresents unique challenges. Although GD includes individuals and family members,family members who may be at risk but who have not been genetically tested may notnecessarily see the relevance of GD to them. Stigma or prejudicial attitudes may occurtowards an HD family, for example, but since GD is commonly regarded as the denial ofopportunities such as insurance or employment, the issue of GD may not be consideredas relevant for members who either have not had a particular experience of GD or whohave not been genetically tested or for those who have tested ‘negative’ (Treloar et al.,2004). Thus, identifying the study population is particularly challenging since individualswho would represent the target population of GD may not necessarily view themselvesas targets of GD.Furthermore, the distinction between an asymptomatic individual from apresymptomatic or once-symptomatic but now asymptomatic person is equally difficult todefine and will likely continue to evolve as the clinical validity of genetic testing andunderstanding of the natural histories of diseases develop. In the context of HDspecifically, for example, the classification of asymptomatic persons continues to evolve51as new insights reveal very early cognitive and psychiatric changes occurring in HDmutation carriers which even precede the unequivocal clinical diagnosis of HD (Duff etal., 2007; Hinton et al., 2007; Johnson et al., 2007; Snowden et al., 2002; Solomon et al.,2007). Likewise, the previous category of ‘asymptomatic’ has evolved to include statessuch as: “prediagnosed”, “preclinical”, or “premanifest” recognizing the continuum ofsub-clinical changes that occur in persons carrying the HD mutation rangingup to 39years from estimated onset of HD (Hinton et al., 2007).The need to sample populations at risk for genetic conditions also presentsissues since sampling frames such as support groups, clinical patients or diseaseregistries may be skewed towards individuals who may be more resourceful and willingto identify themselves. Thus, perhaps, those most vulnerable to GD or those who fearGD most may not be captured by such sampling frames and the extent of the concern orexperience of GD may not be fully ascertained. Moreover targeting sociallyidentifiablesubpopulations at risk for GD entails the risk of stigmatizing them (Foster et al., 1998).Investigating the extent of GD is further challenged by the requirement to baseprevalence estimates on large, community datasets. Thus, high participation of a defined(as opposed to a self-defined, self-selected) population and comparisons of respondersto non-responders is required to appropriately generalize prevalence estimates (Treloaret al., 2004). Ideally such estimates are compared to another population, genetic as wellas non-genetic or general, to achieve a better appreciation of the extent of the issue.2.4 RESEARCH DESIGNA sequential mix method design was selected as a means to meet the challengeof conceptualizing GD, describing the concerns, experiences and strategies of GD aswell as measuring its extent across the population. The philosophical assumption whichunderlies this mixed method study is pragmatism. The focus of the pragmatic paradigmis on a particular research problem. Pragmatist knowledge claims are not committed toone system of approach: they draw on many methods since they are concerned withtheir application and real-world practice (Creswell, 2003).Mixed methods are also warranted as each method addresses a particularaspect of the research question. That is, the nature of GD is explored qualitatively whileits extent is investigated quantitatively. Furthermore, quantitative approaches allowstatistical generalizability and establish relationships between variables, while qualitativeapproaches add rich description and facilitate interpretation of the quantitative findings.52By mixing methods, a triangulation of the data may be achieved to deepen theunderstanding of the nature and extent of GD.PHASE 1: QUALITATIVE STUDY OF THE NATURE OF CONCERNS, EXPERIENCES ANDSTRATEGIES FOR GENETIC DISCRIMINATIONAlthough the definition of GD has been recognized and subjected to considerabledebate by scholars, the concept of GD has not been developed so as to delineate itsconceptual features. Only when a concept’s characteristics, boundaries, preconditionsand outcomes have been defined can the concept be measured (Morse et al., 1996).Existing literature lacks a mature conceptualization of genetic discrimination as well asan understanding of genetic discrimination, from the perspective of persons at risk for agenetic disorder. Furthermore, the strategies used to manage GD are unknown.Qualitative research approaches facilitate the conceptual exploration of otherwiseunexplored phenomena and can generate insights for further development or testing onrepresentative samples (Morse and Field, 1995). Qualitative research approaches arealso appropriate when the intent of the study is to gain insights into the meaning ofexperiences from individuals (Rubin and Rubin, 1995).Grounded theory was used as the qualitative method for this study. The choice ofgrounded theory is appropriate as it is typically used to explore basic social processes(Strauss and Corbin, 1998) based on the theoretical assumptions of symbolicinteractionism (Blumer, 1969). It is also consistent with the assumption that GD issituated in the social interactions and consequences that occur following disclosure ofone’s risk or genetic status. Thus, grounded theory aided the conceptual development ofGD, aided the description of the concerns and experiences of GD and informed thesurvey questions and response options of a genetic discrimination survey specific to HD.PHASE 2: QUESTIONNAIRE DEVELOPMENT, PRETEST AND PILOTPrimary topics of discrimination specific to the HD population identified during theinitial qualitative approach were used to modify an existing version of a GD survey. Theoriginal survey was used to examine the extent of GD across Australia for a range ofgenetic disorders. It lacked specificity and sensitivity to capture the scope of factorsinfluencing GD in this at risk Canadian HD population. A survey instrument was thusdeveloped to assess the perceptions and experiences of discrimination in the proposedpopulation. The developed survey underwent expert critique, oral debriefing and pilot53testing. Details related to the development and content of the questionnaire areaddressed in Chapter 5.PHASE 3: SURVEY ON THE EXTENT OF GENETIC DISCRIMINATION AMONG PERSONS AT RISKFOR HD:A large-scale survey of the at-risk HD Canadian population was undertaken toidentify the prevalence and scope of GD. Details related to the sampling decisions, datacollection and analyses for the survey are presented in Chapter 4.Details relating to sampling decisions, data collection and analyses for eachstudy phase are not addressed in the present chapter. Chapter 3 and 4 address thequalitative methods details and Chapter 5 outlines the quantitative method detailsrelevant for the present study. Accompanying the details of the study procedures inChapters 3, 4, and 5 are 4 appendices: Appendix A (consent forms), Appendix B (semi-structured interview guide), Appendix C (cognitive interview guide), and Appendix D(survey instrument).2.5 ETHICAL CONSIDERATIONSEthical issues are inherent to all research. Such issues may be addressed at theoutset of the study while others can not be anticipated. The following considerationsrepresent the ethical issues which were considered during the planning stages as wellas those that surfaced unexpectedly.Although there is no potential for causing physical harm to participants in thisparticular study, there is a possibility of causing undue stress or psychological harm. Thepossibility of harm exists by virtue of questioning individuals about their perceptions andexperiences of discrimination, an undoubtedly unpleasant experience. Persons areasked to recall, or re-live, experiences that may have otherwise been buried or avoided.If emotional reactions occurred during the data collection the interview was stopped and,if permitted, continued at another time. At the conclusion of each interview the well-beingand need for further support was assessed. A follow up phone call occurred by theresearcher and/or by a clinician if the participant consented to disclose his/her contactinformation. Additional support was offered for any study participant who was interestedin consulting with a health care professional.54Another ethical consideration of the utmost importance is the protection ofparticipants’ sensitive information, especially when dealing with genetic information.Confidentiality issues that concern sensitive data were considered at the outset of thestudy. Several steps were taken to ensure that the information provided by participantswill not compromise their current status of employment, level of insurance and current orfuture level of care. First, all invitations to join the study were prefaced by a statementensuring the individual that their level of care would not be compromised by theirdecision to participate in the study. The interviews were conducted in a secureenvironment (i.e. in private, away from third parties and family members) to allow theparticipants to speak freely. The participants were also ensured that it will not bepossible to identify participants since any identifying information was replaced with anumber on any of the survey instruments or transcribed interviews. Furthermoreparticipants were notified that all data was stored in a secure, locked storage cabinet.Any information collected in the study was only to be seen by the research team and inthe event of publication pseudonyms would be used to protect the identity ofparticipants.Finally, qualitative research methods pose challenges in predicting how and whatdata will be collected. Likewise, there were some ethical issues that were simplyunanticipated. For example, inherent to most participants’ narratives about being at-riskfor HD, included their stories and strategies of how they came to grips with their riskstatus. Although most participants spoke of cognitive strategies and new life plans, oneparticipant described her intent to commit suicide should she become symptomatic in thefuture. Indeed confidentiality could not be upheld in this situation since I had the moralobligation to report her suicide ideation to her physician. After notifying her physician,follow up occurred by the clinic staff to assess the suicide risk and wellbeing of theparticipant. Ongoing support is being provided for this participant in the context of amulti-disciplinary health care team.552.6 REFERENCESAllison K.W. (1998). Stressed and oppressed category membership. In Prejudice: The targetsperspective, J.K.Swim and C.Stangor, eds. (San Diego, CA: Academic),pp.145-1 70.Arboleda-Florez,J. (2003). Considerations on the stigma of mental illness. Can. J Psychiatry 48,645-650.Blumer, H. (1969). Symbolic I nteractionism. Perspective and method. (New Jersey: Prentice-Hall).Creswell,J.W. (2003). Reserach Design: Qualitative, quantitative and mixed methodsapproaches. (Thousand Oaks: Sage Publications).Crocker,J., Major,B., and Steele,C. (1998). Social Stigma and Self Esteem. In Handbook ofSocial Psychology, D.Gilbert, S.T.Fiske, and G.Lindzey, eds. (Boston: McGraw Hill),pp.504-553.Duff, K., Paulsen,J.S., Beglinger, L.J., Langbehn, DR., and Stout,J.C. (2007). PsychiatricSymptoms in Huntington’s Disease before Diagnosis: The Predict-HD Study. Biol. Psychiatry.Foster,M.W., Bernsten,D., and Carter,T.H. (1998). A model agreement for genetic research insocially identifiable populations. Am J Hum. Genet 63, 696-702.Goffman,E. (1963). Stigma: The management of spoiled identity. (Harmondsworth: Penguin).Hinton,S.C., Paulsen,J.S., Hoffmann,R.G., Reynolds,N.C., Zimbelman,J.L., and Rao,S.M. (2007).Motor timing variability increases in preclinical Huntington’s disease patients as estimated onsetof motor symptoms approaches. J Int. Neuropsychol. Soc. 13, 539-543.Johnson,S.A., Stout,J.C., Solomon,A.C., Langbehn, D.R., Aylward, E.H., Cruce,C.B., Ross,C.A.,Nance,M., Kayson,E., Julian-Baros,E., Hayden,M.R., Kieburtz,K., Guttman,M., Oakes,D.,Shoulson,l., Beglinger,L., Duff,K., Penziner,E., and Paulsen,J.S. (2007). Beyond disgust:impaired recognition of negative emotions prior to diagnosis in Huntington’s disease. Brain 130,1732-1744.Jones,E., Farina,A., Hastorf,A., Markus,H., Miller,D., and Scott,R. (1987). Social Stigma: thepsychology of marked relationships. (New York: Freeman).Link,B.G. and Phelan,J.C. (2001). Conceptualizing stigma. Annual Review of Sociology 27, 363-385.Major,B. and O’Brien,L.T. (2005). The social psychology of stigma. Annu. Rev. Psychol 56, 393-421.Miller,C. and Major,B. (2000). Coping with stigma and prejudice. In The social psychology ofstigma, T.Heatherton, R.Kleck, M.Hebl, and J.Hull, eds. (New York: The Guilford Press), pp. 243-272.Morse,J.M. and Field,P.A. (1995). Qualitative research methods for health professional.(Thousand Oaks, Ca.: Sage Publications).Morse,J.M., Mitcham,C., Hupcey,J.E., and Tason,M.C. (1996). Criteria for concept evaluation.Journal of Advanced Nursing 24, 385-390.56Rothstein,M.A. and Anderlik,M.R. (2001). What is genetic discrimination, and when and how canit be prevented? Genetics in Medicine 3, 354-358.Rubin,H.J. and Rubin,I.S. (1995). Qualitative interviewing: The art of hearing data. (ThousandOaks, CA: Sage Publications).Scambler,G. and Hopkins,A. (1986). Being Epileptic - Coming to Terms with Stigma. Sociology ofHealth & Illness 8, 26-43.Sidanius J and Pratto F (1999). Social dominance: an intergroup theory of social hierarchy andoppression. (New York: Cambridge University Press).Snowden,J.S., Craufurd,D., Thompson,J., and Neary,D. (2002). Psychomotor, executive, andmemory function in preclinical Huntington’s disease. J Clin Exp. Neuropsychol. 24, 133-145.Solomon,A.C., Stout,J.C., Johnson,S.A., Langbehn,D.R., Aylward, E.H., Brandt,J., Ross,C.A.,Beglinger,L., Hayden,M.R., Kieburtz,K., Kayson,E., Julian-Baros,E., Duff,K., Guttman,M.,Nance,M., Oakes,D., Shoulson,l., Penziner,E., and Paulsen,J.S. (2007). Verbal episodic memorydeclines prior to diagnosis in Huntington’s disease. Neuropsychologia 45, 1767-1776.Strauss,A. and Corbin,J. (1998). Basics of qualitative research:Techiniques and procedures fordeveloping grounded theory. (Thousand Oaks, CA: Sage Publications).Treloar, S., Taylor, S., Otlowski, M., Barlow-Stewart, K., Stranger, M., and Chenoweth, K. (2004).Methodological considerations in the study of genetic discrimination - A review. CommunityGenetics 7, 161-168.57Chapter 3: The Nature of Genetic Discrimination1A version of this chapter has been published as:Yvonne Bombard, Elizabeth Penziner, Oksana Suchowersky, Mark Guttman, Jane S. Paulsen, Joan L.Bottorif and Michael R. Hayden (2007). Engagement with genetic discrimination: concerns and experiencesin the context of Huntington disease. European Journal of Human Genetics. Advance online: Oct 24 2007.583.1 INTRODUCTIONHuntington disease (HD) is a degenerative neuropsychiatric disorder that usuallypresents in mid-life as a triad of cognitive, psychiatric and movement disturbances. It isinherited in an autosomal dominant manner and is caused by a mutation comprising aCAG trinucleotide expansion in the HD gene (MacDonald et al., 1993). Individualsaffected with HD suffer from mood and personality changes, progressive cognitivedecline and worsening of the movement disorder, which ends in death approximately 15to 20 years from diagnosis (Hayden, 1981). No therapy is currently available to alter thecourse of the disease.The discovery of a polymorphic DNA marker tightly linked to HD (Gusella et al.,1983) led to the first predictive test for an adult onset genetic disease in 1986, allowingat-risk individuals to learn with near complete certainty whether or not they haveinherited the HD mutation (Hayden et al., 1988). Although early surveys indicated thatpredictive testing would be requested by 66-79% of individuals at-risk for HD (Kessler etal., 1987; Mastromauro et al., 1987), worldwide uptake currently ranges between 3%and 24% among at-risk individuals (Creighton et al., 2003). The most frequently citedreasons for declining predictive testing have been the absence of a cure, concerns aboutcoping and the fear of genetic discrimination (Quaid and Morris, 1993).Genetic discrimination (GD) refers to the perceived differential treatment ofindividuals or their family members based on presumed or actual genetic differencesrather than physical characteristics (Billings et al., 1992). Although considerable debatesurrounds the existence of GD in the context of HD (Harper et al., 2004), there is apaucity of research on the nature and experiences of GD among this community.Reports of GD have been documented among a variety of genetic disease communities(Alper et al., 1994; Apse et al., 2004; Armstrong et al., 2003; Billings et al., 1992; Gelleret al., 1996; Hall et al., 2005; Lapham et al., 1996; Low et al., 1998). The anecdotalreport of a teacher in Germany who was deemed unfit to teach only because she was athigh risk for HD focused international attention on this issue (Burgermeister, 2003;Harper et al., 2004). Strategies to manage the risk and experiences of GD have beendescribed (Bombard et al., 2007b). They included “keeping low” (i.e., attempts to pass orcarry on and keeping results private) as well as preempting, minimizing and confronting59GD. These strategies varied depending on the form of the GD experience and thedegree to which individuals engage with (or internalize) GD.The consequences of GD, both for individuals and society, are far-reaching asthey have the potential to create significant social, health and economic burdens bylimiting opportunities for individuals at genetic risk in a range of contexts (Otlowski et al.,2003). Given the likelihood that similar tests will become increasingly available forpredicting risks for other diseases, exploring the nature of GD in the context of HD willbe generally instructive for other disorders. As individuals’ strategies for managing GDappeared to vary in terms of how they constructed their experiences, it would be helpfulto have a better understanding of their initial reactions to GD (or the risk of GD) and howthey make sense of these experiences. The aim of this study was to explore concernsand experiences of GD among asymptomatic individuals from HD families.3.2 METHODSQualitative research approaches facilitate the conceptual exploration of otherwiseunexplored phenomena (Morse et al., 1996) and are also appropriate when the intent ofthe study is to gain insights into the meaning of experiences from individuals. As such,this study aimed to explore the concept of GD as well as the concerns and experiencesof GD. This inquiry was informed by grounded theory, a qualitative research approachtypically used to explore basic social processes (Strauss and Corbin, 1998) based onthe theoretical assumptions of symbolic interactionism (Blumer, 1969). The choice ofgrounded theory is consistent with the assumption that GD is situated in the socialinteractions that occur when presumptions or information about genetic status come intoplay.STUDY SAMPLE AND RECRUITMENTThe approval of the relevant research ethics boards was received to recruitindividuals from three genetic and movement disorder clinics in Vancouver, Calgary andToronto, Canada. To facilitate the exploration of discrimination based on geneticinformation as opposed to symptoms or disability, only individuals who were notdiagnosed with HD were eligible to participate. Symptom status was confirmed withrecent neurological assessments at these clinics. Written and verbally recordedinformed consent was obtained from all participants.Thirty-seven individuals who were found to have the HD mutation (HD+; ‘positivetest result’) were sampled according to purposive sampling procedures where variation60across participant demographic variables was sought (e.g., age, gender, education andtime since genetic testing) and formed the primary sample for this study. Ten people witha family history of HD but who chose not to undergo testing (NT; ‘not tested’), as well aseight people who were found not to have the HD mutation (HD-; ‘negative test result’),were recruited for the purpose of making theoretical comparisons. Theoreticalcomparisons are a vital part of discovering the properties and dimensions in the dataand enable identification of variations in the developed theory (Strauss and Corbin,1998). Inclusion of these comparison cases provides the opportunity to assess howfamily history and ‘negative’ test results influenced concerns and experiences of GD andtested the limits of the proposed theory. Participant recruitment continued until no newthemes developed from subsequent interviews (Strauss and Corbin, 1998).DATA COLLECTIONData were collected through individual, semi-structured, open-ended interviewsconducted by telephone (N=16) and in person (N=39). All the interviews were conductedby the first author and lasted 65 minutes on average (range: 50 - 90 minutes). Theinterviews were digitally recorded, transcribed verbatim and checked for accuracy. Fieldnotes were maintained to document important contextual and behavioural information.During the interviews, participants were encouraged to reflect on the followingissues: their interpretations of GD, their experiences and concerns for GD, their thoughtson genetic privacy, as well as personal, social and other factors involved in theirconcerns and experiences of GD. In view of the sensitivity and potential bias introducedwith the term discrimination, interviews were conducted using its definition, ‘differentialtreatment,’ which enabled participants to reflect on both the positive and negativeaspects of learning about their predictive test results or family history of HD.DATA ANALYSISConstant comparison analysis was used to explore the concerns andexperiences of GD. Interview transcripts were entered into a software program (NVivo 2,QSR International) to facilitate coding and data retrieval. The way in which the groundedtheory analysis was used is described in detail elsewhere (Bombard et al., 2007).3.3 RESULTSSAMPLE CHARACTERISTICSThe characteristics of the participants in our study are presented in Table 3.1.The characteristics of our tested sample appear similar to previous reports of Canadian61adults who receive predictive testing results for HD (Bloch et al., 1989; Creighton et al.,2003). The characteristics of our untested sample appear similar to individuals whochoose not to test, although our untested sample are more educated (Quaid and Morris,1993).CONCERNS AND EXPERIENCES OF GENETIC DISCRIMINATIONIn the course of discussions about GD, participants spoke about their concernsand experiences in a pensive manner, yet with a tone of conviction. At times, non-verbalcues such as hand-gesturing and shifting in their seats were evident among someindividuals, suggesting some discomfort with this potentially sensitive topic. Althoughmost discussions of their concerns and experiences were fairly detailed, someparticipants limited their narratives to matter-of-fact statements (e.g., as in the case ofinsurance GD), not providing much in the way of feelings or details. In addition to theword ‘discrimination,’ participants frequently used other terms such as “issues,”“ramifications” and “adverse consequences” when referring to GD.Individuals reported concerns about and experiences of GD in various formsincluding increased symptom monitoring, communication changes, a perceived lack ofcloseness or support, as well as pressure regarding reproductive, educational andmarriage decisions from relatives. Loss of financial benefits was also linked with GD inthe form of insurance rejection and increased premiums, imposed limits to opportunitiesin the workplace, promotional denials and forced retirement. Perceived differentialtreatment related to HD familial history and genetic test results were also associated withincreased surveillance by employers, experiences of social avoidance and pity as wellas perceptions of altered medical advice by health care professionals. Individuals alsoreported feelings of being “tainted” by their family history of HD in social andemployment situations. A summary of these concerns and experiences is presented intable 3.2.For all of the participants, GD was not an issue they thought about on a regularbasis but one that they considered “occasionally” when an event sensitized them to theissue. Renee (HD-; pseudonyms have been used to protect the identity of participants.)explained: “you’re not constantly thinking about it every moment and you just kind of geton with life and every now and then, you know, something hits you.” Awareness of GDwas precipitated by events that suggested to the participants that having a geneticdifference may have consequences.62AWARENESS EVENTSParticipants became aware of GD through observations of affected relatives’experiences of stigma and discrimination, through information provided by geneticcounselors and through their own experiences of GD. Growing up with a symptomaticfamily member sensitized participants early to HD-related stigma and discrimination.Kate (HD+) recalled the “ignorance” she experienced when members of the public wouldreact to her affected mother by asking: “what’s wrong with her; she’s drunk?” Similarexperiences were reported among the other groups. Tanya (HD-) described herfrustration with how her symptomatic mother was treated as though she were “dumb”and a “homeless person” by those around her, despite efforts to educate others aboutthe disease. Frances (NT) also recalled how her father’s neighborhood ostracized himwhen he began exhibiting the illness, owing to a lack of understanding.Receiving information about GD constituted the second type of awareness event.Genetic counselors were the primary source of this information for participants whoreceived genetic counseling. For example, being advised by genetic counselors to “lookinto” life insurance before proceeding with predictive testing and to be careful aboutdisclosing test results directly highlighted the potential for GD. Participants from allgroups also became aware of the potential for GD from questions on insuranceapplications, reports from social support groups, the HD newsletter and televisionprograms which highlighted particular cases of GD in the United States.Personal experiences of differential treatment constituted the third type ofawareness event. These experiences were most clearly represented among our primarysample (HD+ group) and occurred in five domains: insurance, family, social, health careand employment. Of the 25 individuals who experienced GD, nine describedexperiences of being treated differently in insurance underwriting, being deniedinsurance policies and upgrades. Subtle forms of differential treatment in familysituations also arose that participants related to their real or assumed genetic status.Thirteen individuals described experiences that included altered patterns of interaction,symptom monitoring and events where they felt their test results were used against themby family members. For example, some participants spoke of their discomfort with thefact that their spouses began watching them “like a hawk’ for symptoms of HD afterlearning their test results. In one instance, a single mother recalled an unexpected63encounter with GD during legal proceedings where her test results were “used against”her by her ex-partner as a threat to pursue custody of their daughter.With respect to their social domain, six participants linked experiences ofromantic relationship rejection, social “shunning” and being treated as having a“contagious disease” to their new HD genetic status. In the health care domain, twoindividuals described altered medical advice following disclosure of their HD geneticstatus. One believed that the advice she received that her daughter should not havechildren if genetic tests were positive for HD was insulting. The other was frustratedwhen her physician attributed her current, unrelated medical issues to her genetic testresult for HD and did not manage her symptoms with the attention she felt theydeserved.The most blatant forms of discrimination were reported to have occurred in theworkplace by five participants. The participants believed that the information about theirgenetic status was directly related to unsuccessful bids to get a promotion, imposition ofan unwanted early retirement and increased surveillance by their employers. Forexample, Michelle, a healthcare professional, felt singled out because of her genetic testresults when her supervisor requested access to her medical files so that her employerscould “monitor” her for symptoms “faster, easier than taking [her] word for it”. Awarenessevents like these prompted individuals to begin a cognitive and emotional process ofengagement with GD as a preliminary step toward attending to their feelings offrustration or concern and determining their risk and consequences of GD.THE CONCEPT OF ENGAGEMENT WITH GENETIC DISCRIMINATION (GD)Engagement with GD describes a cognitive and emotional process individualsused to interpret the meaning of GD and personalize its risk and consequences in theirlives. The process of engagement is precipitated by awareness events and results inpersonal formulations of the risk and effects of GD. Engagement with GD provides aframework to understand individuals’ perceptions and experiences of GD as well as theirreactions to and strategies for GD. Each phase of engagement with GD and factors thatinfluenced this process is described in more detail in the following sections. Examplesreflecting differences in the engagement process between the groups are highlightedwhere appropriate.64STATES OF ENGAGEMENT WITH GENETIC DISCRIMINATION (GD)On the basis of differences observed among participants, three broad states withrespect to engagement with GD were identified: engaged, disengaged and resistingengagement. The state of engagement with GD was directly influenced by one’s geneticstatus and risk perception for HD. Although all the participants in our study were at riskfor HD at some point in their lives (i.e., they were “all in the same boat”), the way inwhich they engaged with GD either with respect to their family histories or their genetictest results varied with their genetic status and risk perception for HD. Individuals whochose not to undergo genetic testing (NT) usually thought about their risk for developingHD with a certain degree of optimism or pessimism. Untested participants who spoke asthough they had the HD mutation (pessimistic bias) engaged with GD in similar ways toHD÷ participants. In contrast, participants who held an optimistic bias (low perceived riskfor HD) normalized their genetic risk for HD arguing that they are no different thancolleagues or members of their social circles who have family members suffering fromother common disorders. Anna (NT) alluded to this: “I’m thinking well, yeah, I’m apotential risk [but] so is the guy next door; he could die of a heart attack tomorrow, youknow.” They did not believe that their family history of HD necessarily set them apartfrom others. They also maintained a position that they were just as likely not to have theHD mutation as to have it. Hillary (NT) explained: “I choose to look at it that there’s a fiftypercent chance that I’m not going to get it and there is no more chance that I will.” Thusthey perceived that their risk for GD is no different than the general public and deflectedthe need to engage with GD. Hannah asserted: “I don’t go there, I don’t think about it...acknowledge the existence of it and that’s about it.” Thus some untested participantswho held an optimistic bias were able to deflect the need to engage with GD, andultimately, resisted engagement.Individuals who underwent genetic testing were required to engage with GD aspart of the informed consent process. However, those who learned that they did nothave the HD mutation were able to disengage themselves from GD as they were nolonger at risk for HD. They discussed their ability to “un-attach” themselves from “thebaggage of HD” or “remove the stigma of the disease” by “reinforcing” their “negative”test results to others. After learning of their results, these individuals simply disengaged65themselves from GD because they felt that GD was a “non-issue”, as they consideredthemselves “normal.”Ultimately, four groups can be discerned from the categorization of engagementalong the dimensions of their risk perception and genetic status for HD: testedindividuals who had the HD mutation (HD+), tested individuals who did not to have theHD mutation (HD-), untested individuals who held a pessimistic bias about their HD risk(NT-P) and untested individuals who held an optimistic bias about their HD risk (NT-O).Essentially, all groups except for the latter engaged with GD (Figure 3.1). It is importantto note, however, that individuals’ genetic status for HD and risk perception is not a staticstate. HD- participants, for example, spoke about past experiences of stigma anddiscrimination based on their family history despite the fact that they were in a position todisengage with GD. Likewise, one’s risk perception for HD can presumably fluctuateover time. Categorizing participants along these dimensions, nonetheless, was helpful inillustrating how one’s genetic status and risk perception at the time of their particularawareness event influenced the way in which they engaged with GD.THE PROCESS OF ENGAGEMENT WITH GDEngagement with GD involved two phases. Initially, individuals formedmeaningful interpretations of GD by making sense of GD, defining its various forms andvalidating the threat of GD. In the second phase, individuals personalized GD todetermine its risk or consequences for themselves or their families. They did this byconducting a mental survey - taking into account their social, financial, employment orfamilial circumstances as a way of assessing their potential for GD or of understandingthe consequence of a particular GD experience. Emotional reactions often ensued in thecourse of engagement, which included feelings of concern, irritation, anger, frustration orindifference.FORMING MEANINGFUL INTERPRETATIONS OF GDThe phase of forming meaningful interpretations of GD occurred when individualsbegan to reflect on what they learned or experienced that raised the issue of GD. Threethemes in the data describe the cognitive strategies used: assigning meaning, definingforms of GD and validating the threat of GD.Assigning Meaning: As most participants attempted to make sense ofawareness events, they did not immediately label them as ‘genetic discrimination.’Rather they associated GD with notions of “exclusion,” “restricting access,” “disallowing,”66“being prevented from doing something,” “isolation” and “unfair treatment.” For theparticipants who engaged with GD, differential treatment consisted of both positive andnegative forms, but discrimination was regarded as a negative, “stronger” form ofdifferential treatment.Participants invoked human rights issues and shared strong reactions as theyattempted to makes sense of negative forms of differential treatment. Scott (HD-i-)deemed employment GD as “totally unfair, illegal, and happropriate, a travesty which weas a society shouldn’t accept.” Kerry (HD-) interpreted insurance and social GD as“horrible negative treatment, having something taken away based on a birth defect.”Participants likened differential treatment related to genetic status to other types ofdiscrimination based on ethnicity or religion which were similarly “unethical.” Patrick(HD+), for example, explained why his GD experiences werea “definite Charter [ofRights and Freedoms] issue:”From a legislative point of view, discrimination based on genetic testing... is nodifferent than discriminating against somebody who’s a visible minority or [has] ahandicap, you know, because right now you can’t, under the Charter [of Rightsand Freedoms], you can’t discriminate against people because of a disability,right? So do I have a disability? Right now, today, no, but I’m being discriminatedagainst.Prejudice and stigma were elements highly intertwined in participants’interpretations of GD. Hillary (NT-P) explained the moral underpinnings of GD when sheasserted, “They’re disallowing people for things that have not affected them yet. Yeah, /think that’s absolutely prejudicial.” Kerry (HD-) recounted her thoughts about GD beforereceiving her test results and described these consequences as “stigmatizing:”I get energy from people. So to take that away from me, you’re draining me andby stigmatizing me, isolating me, singling me out, you are taking that away fromme. So for me that would be, that would be a very horrible thing, I would hatethat.Defining Forms of GD: Participants’ interpretations of GD also included definingthe various forms of differential treatment related to genetic status: actual or perceivedand interpersonal or institutional forms. Actual GD was characterized by participants ashaving “proof’ of a GD event whereas perceived GD was associated with the absence ofobjective evidence. Patrick (HD+) used this distinction to conceptualize his GD67experiences of being required to pay increased life insurance premiums and havingbeen denied a promotion.It’s actual [discrimination] because the insurance company is asking have youbeen tested for Huntington’s disease or has any family member been tested forHuntington’s. That’s not perceived. That’s actual because it’s written on... the[insurance] forms. So perceived discrimination is ... where I think it impacted in asignificant way the decision of me not getting that position, [but] I could becompletely wrong.Some individuals also drew a distinction between institutional and interpersonalGD. Interpersonal forms of GD, underpinned by “personal interaction” and “emotions,”occurred in family and social environments. This contrasted with institutional forms ofGD such as in the workplace, courts, adoption, health care or insurance industry, whichlacked an emotional basis.Validating the threat of GD: Concepts of rights, fairness and rationality wereused by participants to validate GD. Participants’ interpretations of GD were foundedupon a perception that genetic information is inherently special. Individuals regarded thisinformation as “personal’ and therefore it did not need to be shared. Accordingly,participants believed that insurance companies and other third parties had no right” totheir genetic information and questioned the fairness of denying or terminating insurancecoverage on the basis of predictive test results.Others who focused on the “unfairness” of being treated differently by insurersthought that they should not be penalized for things over which they have no control. Asone participant explained, “It’s the luck of the draw and unfortunately I’ve got thedefective gene so it’s not my fault that I got it [HD mutation] but you [insurer] shouldcover me.” Paul (HD-) believed that using genetic information in hiring practices wouldbe “unfair” and have widespread consequences:There’s so many tests for genetics these days and would an employer.., havethe right then not to hire you based upon that? ... I think probably because testinghas got so specific and accurate now to identify these things, it’s [GD] probablyunfair because . .. it could affect thousands of people too, you know, look at thenumber of identified genetic diseases, that could affect an awful lot of people.68PERSONALIZING THE RISK FOR AND CONSEQUENCES OF GDThe second phase of engagement with GD included participants’ efforts todetermine how GD may affect them or their families as wellas their emotional responsesto GD. Participants conducted a mental survey of their personal circumstances to predictor imagine the consequences of having a genetic difference.Although some participantsengaged with GD to attend to their feelings of concern or anxiety, othersdescribedconcern or indifference as a result of personalizing the risks and consequencesof GD.Conducting a mental survey: Participants used a ‘factoring in’ process in whichthey systematically reviewed their current and future circumstances to makethe bestpossible assessment of their potential for GD. They placed emphasis on thosecontextspotentially affected by their genetic status, such as insurance policies,workplaceenvironment and interpersonal relationships. Patricia (HD+) recalled explicitlysurveyingher current circumstances: “I took my time to stop and think about this whole thingThe people you work for and your family, you know your associates...especiallyinsurance.” She explained how her ‘factoring in’ process tooka few months, “I wanted tocover all my bases and do research and find out what coverage I had, what benefitsIhad, what I would lose if / told anybody.” However, uncertaintiesabout possiblereactions by others often complicated this mental survey. In thinking about his potentialfor GD at work, Wesley (HD+), a married father and corporate executive,characterizedhis efforts to determine his personal risk for GD as a ‘struggle.’ He said:I struggled a lot... I thought about ... taking on a new job which I’ve just recentlydone... should I tell somebody that I have this condition that in five years timemight affect me and all of that and I said, you know what: “no.”Similarly, Kerry (HD-) explained her ‘factoring in’ process before predictivetesting and described the consequences of GD as “horrible”:I’d thought about insurance and I knew... that I would be at risk, that my jobwould be at risk that my ability to get insurance would be at risk which would, inmy view, would put my family at risk if I couldn’t be insured and that wasahorrible, horrible feeling just knowing that, because you’re treated, you’re treateddifferently if you have this [HD mutation].”In conducting this mental survey, participants relied upon their experience.Individuals sometimes ‘factored in’ their experiences of public reaction to other diseases69in personalizing their risk for GD. Brendan (HD+) considered how lack of publicunderstanding about HIV/AIDS affected the way people with the disease were treated tosupport his concerns about GD. He recalled:Ignorance breeds fear as people do not understand something, then they fear itand if they fear it, then, yes, they’re going to treat you differently. I mean aperfect example of that is, is people with AIDS and how that was handled whenwe didn’t understand how that disease was transmitted from person to person.Individuals reflected on both positive and negative experiences in theirassessment of their potential for GD. Although increased support, empathy andacceptance were recognized as positive experiences following predictive testing,participants dwelt on the impact of negative experiences.Reacting to the risk and consequences of GD: Personalizing GD involved arange of emotional reactions that informed the way individuals internalized theconsequences of GD. These included feelings of concern, irritation, anger, frustrationand indifference. Concern, however, was the predominant emotion expressed byparticipants for themselves and, particularly, for their children. Ethan’s (HD+) concernabout the possible implications of his genetic test result for his children are reflected inthe following quote: “I suppose the possibility of people who do understand the geneticsof it are going to look at my three kids and say, “There’s one in half of them right there,wonder which ones?”The nature of concern for GD was wide-ranging but centered on a feeling ofvulnerability. Rachel’s (HD+) sentiments of employment insecurity were typical:Any mistakes that I make or anything might be blamed on that or you know mightbe “Oh well, you know, it’s because she’s got that gene”.... I think it could be usedas a you know as a reason or an excuse to not promote me further if anopportunity like that were to arise, you know, and worrying, you know well, “Is itsafe to give that job to her because you know, you know she might not be allthere?”Similarly, Paul (HD-) recalled feeling vulnerable because of his HD family history:70There was never any chance then [before testing] of changing [jobs] because Ifelt if I went to another employer that to give them that information [family historyof HD], there’s a lot of issues over ... [and] I wasn’t willing to take a chance at asecure job.In the social context, individuals were concerned about: being “looked atdifferently,” being judged or socially rejected and bearing the brunt of “adversereactions.” Brendan’s (HD+) cautious approach in social settings reflects his concern forbeing stigmatized:Huntington’s is something that I would be concerned to just blurt out in a socialsetting because it would change the way people think.... I mean that wouldchange things immensely.... that would absolutely change how people deal withme.Individuals also indicated concern for future isolation and decline of current levelsof family support and altered medical care. Rachel, for example, was apprehensiveabout how knowledge of her HD status could bias her physician’s clinical assessments:But even in my doctor’s.... I’d rather that, you know, that if he at some pointneeds to determine that I’m symptomatic or not, that he’s making that from apurely clinical point of view.Indifference usually ensued when individuals determined that they wereprotected in some way from the effects of GD. Zara (HD+) explained why she wasindifferent:Afterwards I felt well, I really don’t give a damn because I’m covered. You know,where I worked, the people are good. I’m not going to lose any pay. I’m not goingto lose any of my benefits. My Blue Cross or hospitalization coverage ismaintained throughout... so I don’t have to worry.FACTORS INFLUENCING THE DEGREE OF ENGAGEMENT WITH GDIndividuals engaged with GD to different degrees depending on various factorswhich served to facilitate or impede the process. Individuals who engaged with GD to agreater extent acknowledged the relevance of GD and directly attended to its potential orexperience in an active manner. Frequently individuals highly engaged with GD71described strong emotional reactions. In contrast, participants who engaged with GD toa lesser extent did not actively reflect upon the experience or its potential, and neitherdid they make strong connections between their experiences and GD. Two factors had amajor influence on the degree of engagement with GD: stage of life and the nature of theawareness events.Stage of life: Individuals’ engagement with GD fluctuated over time as their livesand family circumstances evolved. Participants in the earlier stages of building theirlives, with young families, entering new careers and still building relationships, forexample, engaged actively with GD. In contrast, those for whom most life building eventsoccurred before learning of their genetic status or risk for HD perceived GD as lessrelevant, as reproductive, financial and career decisions were already set in place.Nature of the awareness events: Participants who became aware of GD in adirect manner engaged with GD to a greater extent. During genetic counseling sessions,for example, patients are routinely prompted to consider the psychosocial impact ofpredictive test results. Warnings received from genetic counselors during predictivetesting sessions raised alarms for Zara (HD+):You get so many warnings when you’re in counseling. They tell you don’tdisclose this to outside members of the family, don’t disclose this to yourinsurance, don’t disclose this to your employer, don’t disclose it to so manyareas, you know, and that’s why I was concerned because I thought ooh whatam I going to do?In contrast, those who became aware of GD through an indirect or emotionally-neutral event such as through information obtained in a newsletter or support groupengaged to a lesser degree with GD.3.4 DiscussioNOur findings demonstrate that a majority of genetically tested and untestedindividuals in this HD sample are concerned about and experience GD across a widevariety of contexts. This study introduces the psychosocial process of engagement withGD and provides insight into at-risk persons’ perceptions of what constitutes GD.While our results support previous surveys that explored the existence of GD inthe domains of insurance and employment (Apse et al., 2004; Armstrong et al., 2003;72Geller et al., 1996; Lapham et al., 1996; Low et al., 1998), our study is the first to providea detailed description of the concerns and experiences of GD in the HD population, andat the same time to extend the context of GD to include family, social, government andhealth care settings. Although changes in family relationships have previously beennoted to occur after predictive testing for HD (Sobel and Cowan, 2000) this reporthighlights the fact that individuals link disrupted interactions and patterns of behaviourwithin the family with discrimination. Although discriminatory experiences have not beentypically linked to family interactions, this form of GD needs to be considered along withmore obvious forms of GD related to insurance and employment.Most importantly, the study offers an insight into the cognitive and emotionalprocess of engagement with GD aimed at interpreting the meaning of GD andpersonalizing its risk and consequences. Although other studies indicate that patientslearn about GD from news media (Apse et al., 2004; Hall et al., 2005) as well as throughtheir own experiences (Hall and Rich, 2000), the majority of participants in our studybecame aware of GD through interactions with genetic counselors. Indeed, in a study of25 US genetic counselors, 96% routinely discuss GD in cancer genetics (Pfeffer et al.,2003). An inherent tension exists, however, where, in the process of informing theirclients of the potential risks and benefits of genetic testing, genetic professionals may beinstilling an unconfirmed perception that GD exists or is widespread. Coupling theprovision of information about GD with opportunities for clients to discuss concernsabout and past experiences with GD is likely to be helpful in supporting the process ofpersonalizing the factual information presented about GD and identifying strategies tominimize or manage the consequences of GD (Bombard et al., 2007b). The frameworkof engagement with GD provides clinicians with a helpful tool to understand andcontextualize clients’ experiences and may help identify areas where more educationand support are needed.Our findings suggest that individuals regard GD in relation to HD as a basichuman rights issue grounded in concepts of privacy, stigma and prejudice. Included inindividuals’ interpretations of GD were taxonomies and validations that resonate closelywith others’ conceptualizations based on rationality and social acceptability (Otlowski,2005; Rothstein and Anderlik, 2001). Many of our participants reasoned that increasinglife insurance premiums is a form of rational and legal discrimination, yet it remainssocially unacceptable. This particular discord lies in the balance of whether one73considers life insurance a commercial or social good (Lemmens, 2000). In a culturalcontext where universal health care is considered a social right, one may question theexistence of equality when access to commercial goods such as mortgage insuranceand small business loans rely increasingly on life insurance eligibility. Given our findingsof life insurance and promotional denials, social avoidance and altered medical advice, itappears that opportunities are indeed being limited for these individuals. Thus, formerwarnings of a looming ‘genetic underclass’ (Billings et al., 1992) may become a real risk.Engagement as the overarching concept in explaining how individuals interpretedand personalized GD in this study is supported by recent studies developed in relation togenetic risk for HD and hereditary nonpolyposis colon cancer (HNPCC) (McAllister,2002; Taylor, 2005b). Although research by McAllister (2002, 2003) and Taylor (2005)contribute important conceptual understanding about the process of engagement in thecontext of genetics, their conclusions did not serve as theoretical frameworks for thepresent study. Taylor’s (2005) use of the concept of engagement to describe varyingdegrees of openness and involvement in HD genetic test decision making observedamong at-risk individuals is not directly related to this study. In her insightful contribution,McAllister’s (2002) theory of engagement in relation to genetic risk for HNPCC is basedon findings that the degree of cognitive and emotional involvement with individuals’ riskfor cancer varied from partial to intense over time with the unfolding of critical events infamily life (McAllister, 2002). McAllister’s theory of engagement and the engagementwith GD theory proposed in this study both involve cognitive and emotional processeswhich are precipitated by critical events (life events in relation to engagement withgenetic risk and awareness events in relation to engagement with GD). Likewise, thedegree of engagement with cancer risk and GD influences approaches and reactions(McAllister, 2002) as well as strategies (Bombard et al., 2007b) regarding one’s risk forgenetic risk or GD, respectively. The relationship between engagement with GD and riskperception is also similar to that described by McAllister (2003) with individuals’ beliefsabout carrier status linked to their engagement with genetic risk (McAllister, 2003).Although McAllister’s theory did not suggest a direction of the causal link betweenengagement status and beliefs about carrier status, the results of the present studysuggest that pessimistic biases toward being an HD carrier promoted engagement whileoptimistic biases toward not carrying the HD mutation hindered engagement, at leastwithin the context of GD.74There are also important distinctions in the contexts and concepts of thesetheories. McAllister’s (2002) theory of engagement related to genetic risk was developedin the context of studying individuals at 50% risk of carrying the HNPCC mutation beforeand after undergoing predictive testing. However, the theory of engagement with GD isbased on data provided by genetically tested as well as untested individuals from HDfamilies and refers to engagement with genetic discrimination. The contexts of HD andHNPCC are notably different in the degree of validity of the test results as well as thenature, penetrance and management of the diseases.There are also important differences between the concepts of genetic risk andgenetic discrimination. Genetic risk for a future disease presents individuals withinformation about their personal susceptibility and the challenge of understanding andassimilating this information into their self-image. Although this experience is influencedby emotions (Klein and Stefanek, 2007) and family contexts (Cox and McKeNin, 1999;McAllister, 2002), the focus is on the way that risk information shapes individual lives.Genetic discrimination, on the contrary, is grounded in social interactions andrelationships and requires individuals to make sense of others’ reactions and their ownresponses to them. Ultimately one may view engagement with genetic risk as anecessary step toward engagement with GD: individuals may engage with disease riskwithout ever engaging with GD. Our findings provide further support for McAllister’s(2002) theory of engagement and extend the theory to the context of HD and GD.Clearly engagement appears to be an important concept which requires furtherexploration and development in other contexts.There were several limitations in this study that should be considered in theinterpretation of our findings. First and foremost, participants who take part in researchstudies are a self-selected group (Codori et al., 1994) that differs from individuals whodecline to participate in terms of their perspectives and experiences of GD. Given thatGD is one of the reasons individuals at-risk for HD do not participate in predictive testing(Quaid and Morris, 1993), it is possible that we have not fully captured at-risk persons’experiences and concerns for discrimination. As a consequence of our sampling andtimeframe for recruitment only one untested man was available and volunteered toparticipate in our study. This artifact may support previous suggestions that men canhave difficulty in accepting implications of being at risk and cope by using denial (MaatKievit et al., 2000). In addition, because the sample consisted of individuals from the HD75community, the study findings may not necessarily apply to other genetic and non-genetic populations. However, with GD cited as one of the main reasons againstpursuing predictive testing for HD, individuals from the HD community may be a well-suited population in which to explore these issues. These data are based on self-reports,which rely on individuals’ perception of the events that occurred and how they felt theywere treated on the basis of their genetic status. In counseling, however, it is the clients’perceptions that are important, and thus these findings provide counselors a frameworkto understand and contextualize the experiences and concerns that clients share withthem. It is also acknowledged that the data were based on experiences from a Canadiansample whose concerns and experiences may not apply to other populations wherehealth-care funding is privatized.In conclusion, this qualitative study focused on the concerns and experiences ofGD which were grounded in the experience of HD families and may provide a usefulframework for understanding individuals’ concerns, experiences and management of GDin other contexts. These results help identify areas where more education and support isneeded and provide direction to counselors supporting their clients as they struggle withissues of GD and genetic testing.76PRIMARY SAMPLE COMPARISON CASES TOTALParticipants with HD Participants without Participants who haveMutation (N=37) HD Mutation (N8) Not Tested (N1O) (N55)N % N % N % N %GenderFemale 23 62% 5 63% 9 90% 37 67%Male 14 38% 3 38% 1 10% 18 33%Marital StatusMarried/common-law 23 62% 6 75% 8 80% 37 67%Single/separated/divorced/widow 14 38% 2 25% 2 20% 18 33%EducationSome college&above 31 84% 8 100% 9 90% 48 87%Highschool & below 6 16% 0 0% 1 10% 7 13%EmploymentEmployed 26 70% 6 75% 10 100% 42 76%Unemployed 11 30% 2 25% 0 0% 13 24%ChildrenHave children 27 73% 6 75% 7 70% 40 73%Have no children 10 27% 2 25% 3 30% 15 27%Time since Testing0-4 years 9 24% 2 25% -- 11* 41%*5-9 years 16 43% 1 13% -- 17* 63%*10-14 years 10 27% 3 38% -- 13* 48%*15-20 years 2 5% 2 25% -- 4*15%**Based on Tested Sample (N=27)Table 3.1 Sample demographics77PRIMARY SAMPLE COMPARISON CASESHD+ HD- NTTOTAL(N=37) (N8) (N10)(N=55)Concerns Experiences Concerns Experiences Concerns Experiences Concerns ExperiencesN N N N N N N NOverall 28 25 4 5 5 5 37 32Family 4 13 0 4 0 1 4 19Insurance 16 9 2 1 3 4 21 14Employment 19 5 3 3 3 0 25 8Social 11 6 1 0 1 1 13 7Health Care 3 2 0 0 0 03 2Government 0 0 0 0 0 20 2(i.e. adoption,blood_bank)Table 32 Proportion of concern and experiences of genetic discrimination(Categories are not mutually exclusive; participants may have spoken aboutexperiences/concerns under various domains.)78ti Pessimistic__________Bias -mpnFigure 3.1 States of engagement with geneticdiscrimination in relation to geneticstatus and risk perception for Huntington diseaseFamily Historyof Ff0ilGeneticTestingI1• Engagement• Mutatióñ:. - with GD793.5 REFERENCESAlper,J.S., Geller,L.N., Barash,C.l., Billings, P.R., Laden,V., and Natowicz,M. 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New Genet Soc. 23, 225-239.82Chapter 4: The Strategies used to Manage GeneticDiscrimination1A version of this chapter has been published as:Yvonne Bombard, Elizabeth Penziner, Joji Decolongon, Mary-Lou Klimek, Susan Creighton, OksanaSuchowersky, Mark Guttman, Jane S. Paulsen, Joan L. Bottorif and Michael R. Hayden (2007). Managinggenetic discrimination: Strategies used by individuals found to have the Huntington disease mutation.Clinical Genetics 71, 220-231.834.1 INTRODUCTIONHuntington disease (HD) is an autosomal-dominant neurodegenerative disorderthat usually presents in adult life with cognitive, psychiatric and motor disturbances. HDhas a prevalence of approximately 5-10 per 100,000 and is inexorably progressiveending in death approximately 15 to 20 years from onset (Harper, 1981; Hayden, 1981).New approaches to treatment are being explored; however a cure or therapy does notcurrently exist to alter the course of the illness.The discovery of an expanded CAG trinucleotide repeat as the underlyingmutation that causes HD led to the availability of direct predictive testing (MacDonald etal., 1993). The introduction of predictive testing for HD has led to a new group ofindividuals found to have the HD expansion who are currently asymptomatic yetdestined in all likelihood to become affected at some point in the future (Langbehn et al.,2004). Individuals identified with the HD expansion have a CAG repeat length over 35and are considered at ‘increased risk’ for developing HD in their lifetime, should they livelong enough (Kremer et al., 1994). In fact, there is a significant inverse relationshipbetween CAG repeat lengths and age of onset of HD with a larger CAG expansionassociated with an earlier age of onset (Langbehn et al., 2004). Some individuals withrepeat lengths between 36-39 may never develop symptoms of HD in their lifetime, evenif they live to an advanced age as CAG expansions between 36-39 are in the affectedrange but are not fully penetrant (Langbehn et al., 2004; Rubinsztein et al., 1996). WhileCAG length is the major determinant of the age of onset, other genetic andenvironmental factors are also likely to contribute to the variance in age of onset of HD(Rosenblatt et al., 2001).The advent of predictive testing for HD introduced many opportunities as well aspotential challenges for individuals at risk for HD. One potential consequence ofpredictive testing is genetic discrimination. Genetic discrimination (GD) refers to thedifferential treatment of individuals or their family members based on presumed or actualgenotypic difference rather than phenotype (Billings et al., 1992).There have been four reports of genetic discrimination in the context of HD(Burgermeister, 2003; GeIler et al., 1996; Kenen and Schmidt, 1978). Kenen andSchmidt (1978) warned of the dangers of stigmatization of individuals found to have theHD expansion. Although testing was not available at that time, they speculated that atrisk individuals live their lives in a “suspect state”, neither fully stigmatized nor“considered fully normal as the label of defective individual lurks in the background”84(Kenen and Schmidt, 1978). Predictive testing, they presumed, would replace thisuncertainty with social stigma and limit opportunities of these individualsas a result oftheir future illness. A survey of 27,790 individuals and children at risk for geneticdisorders discovered 276 reports of GD among the 623 HD respondents (Geller et al.,1996). Of the 206 follow-up verification interviews conducted 5cases concerneddiscrimination against individuals at-risk for HD. These reports included: life insurancerejection, coercion by a physician to undergo prenatal genetic testingand abort anaffected fetus, 2 cases of adoption denials and a job refusal for the US Air Force (Gelleretal., 1996).An informal poll in Canada found frequent unreported instances of geneticdiscrimination because of a family history of HD or based on predictive testing (Harper etal., 2004). Furthermore, three individuals reported employment difficulties followingdisclosure of their genetic test results to their employers (Harper et al., 2004). The recentcase of a teacher in Germany who was refused a job because of being at risk for HD(Burgermeister, 2003) lends credence to the potential for such discrimination in the HDcommunity worldwide.Fears of genetic discrimination have precipitated altered behaviour aroundpredictive testing for HD including the request for anonymous predictive testing. Severalindividuals have sought predictive testing under anonymity in fear of geneticdiscrimination for themselves and their families in Canada, the UnitedStates and Europe(Burgess et al., 1997; Harper et al., 2000; Maat-Kievit et al., 2000; Visintainer et al.,2001). The selective disclosure of genetic risk information for fear of discrimination hasalso been reported as another strategy to avoid potential loss of opportunities in theemployment context (Australian Law Reform Commission & Australian Health EthicsCommittee, 2006). Finally, withholding information about seeking HD predictive testingfrom health care providers has been previously shown as another method of limitinginsurance or employment discrimination (Williams et al., 1999).While limited evidence for genetic discrimination in the context of HD exists(Burgermeister, 2003; Geller et al., 1996; Harper et al., 2004), little is known about howindividuals found to have the HD expansion manage the potential for or experiences ofgenetic discrimination. Insight into the coping strategies used to deal with geneticdiscrimination can offer approaches for other persons at risk for late onset disorders. Wehave conducted this qualitative study to explore how individuals found to have the HDexpansion manage the risk and experience of genetic discrimination.854.2 METHODSThis study aimed to explore the strategies individuals use to manage the risk andexperience of genetic discrimination. As such, the grounded theory method wasappropriate as it is typically used to develop a theory of a process or interaction inresponse to a phenomenon, ‘grounded’ in the views of participants (Creswell, 2003).This qualitative research approach is characterized by simultaneous data collection andanalysis. The developed theory is based on constant comparison of data with emergingthemes from subsequent interviews. Further data collection and sampling are based onthe emerging analysis, aimed at maximizing the similarities and differences among thedeveloping patterns. Thus, it is an iterative process of moving between data collection,theorizing/conceptualizing and sampling based on emergent patterns (Strauss andCorbin, 1998).RECRUITMENT AND PARTICIPANTSAsymptomatic individuals found to have the HD expansion were recruited bymailed invitation from three HD clinics across Canada. Asymptomatic status wasconfirmed with recent neurological assessments at these clinics. No other exclusioncriteria were used for study eligibility. Variation across time since testing, age, gender,marital status and education level was sought, which is in accordance with purposivesampling for grounded theory research. Recruitment continued until data emerging fromsubsequent interviews achieved adequate saturation of the themes (Strauss and Corbin,1998) which was determined when no new information emerged during the analysis.This study received the approval of relevant research ethics boards. Written and verballyrecorded informed consent was obtained from all participants.DATA COLLECTIONThirty-seven individual semi-structured interviews were conducted by telephone(N=14) and face-to-face (N=23), digitally recorded and transcribed verbatim. Interviewsconducted by telephone and face-to-face did not vary in overall length or quality,consistent with other qualitative research (Janofsky, 1971; Sturges and Hanrahan,2004). All interview transcripts were reviewed and checked for accuracy.An interview guide was developed to reflect the research questions. It was basedupon literature on genetic discrimination and prior research on the concerns of personswho are at increased-risk for HD. Acknowledging the sensitivity and potential biasintroduced with the term ‘discrimination’, the interview guide did not use the word86discrimination rather its definition, differential treatment. This term allowed theparticipants to reflect on their responses to the potential or experience(s) of GD in anopen and non-directive way. Participants frequently alluded to GD using terms such as“issue”, “ramifications” and “adverse consequences.”The interview topics included: experiences with and concern for differentialtreatment in the family, social, insurance and employment domains, as well as factorsinfluencing the use of particular strategies to manage GD. Some of the questionsincluded: what are your experiences in obtaining or keeping life insurance since learningof your test results? Can you tell me what you decided about telling people at work aboutyour test results and how this went? What do you believe would happen if your employerknew of your test results? How has having predictive testing changed things in yourfamily? Follow up probes were used to encourage fuller descriptions and emotionregarding participants’ strategies for their concerns and experiences. (The interviewguide was continually revised as data collection and analysis continued and theresearchers’ understanding of the theoretical concepts developed.)Interviews lasted 65 minutes on average (range: 50-90 minutes). At theconclusion of each interview the well-being and need for further support was assessed.Fieldnotes were maintained following each interview to document what the participantsspoke about, their behaviour, intonation, emotional responses, the interviewer’s (YB)initial impressions on the results and directions for follow-up.DATA ANALYSISA grounded theory approach with constant comparison analysis was used toexplore how participants managed the potential for or experience of geneticdiscrimination. The analysis process included 3 sequential steps: (a) open coding, (b)axial coding, and (c) selective coding. The analysis began by examining the text andidentifying descriptive labels for the data. This process fractures the data into the majorideas brought up by the participants. These first-level codes were condensed andconceptual labels (categories) were generated (e.g. take action in advance to avoid GD,ignoring a GD experience). A coding framework was developed to enable identificationof recurrent categories discussed by the participants. Following the initial process oftaking the data apart, relationships were explored between the categories in the form ofcauses, consequences and interactions to generate a theoretical model (referred to asaxial coding). During this stage, questions and comparisons were made among conceptsand new data to facilitate the discovery of patterns and variations among the data87(referred to as ‘constant comparison’). The final analytic step of selective coding involvedintegrating all the categories under a core abstract category or central phenomenon (e.g.managing GD) which connects all categories together to build a theory.A computer-assisted qualitative data analysis program (NVivo 2) was used tofacilitate coding and management of the interview data. Rigor was established by theuse of member-checking where developing themes and theory were presented toparticipants for verification throughout the analysis. The coding framework anddeveloping theory was also presented to experts in the field for further validation. Finally,recursive questioning during interviews also contributed to data validation.4.3 RESULTSPARTICIPANT DEMOGRAPHICSThe demographic characteristics of the 37 participants are illustrated in Table 1.These characteristics are similar to previous reports of Canadian adults seekingpredictive testing and were found to have the HD expansion (Almqvist et al., 2003). Infact, previous studies have reported an excess of females seeking predictive testing forHD (Almqvist et al., 2003; Creighton et al., 2003; Harper et al., 2000; Maat-Kievit et al.,2000; Mastromauro et al., 1987). Thus, this sample appears representative of individualsamong the HD population who receive increased risk predictive testing results inCanada. Furthermore, this sample is highly similar to the general population in mostdemographic variables, although it is less ethnically diverse (97% vs 87% Europeandecent) and slightly more educated (89% vs 77% high school graduates) (StatisticsCanada Housing, 2002; Statistics Canada Housing, 2003).DIMENSIONS OF THE GD STRATEGIES MODELIn the course of discussions on GD it became evident that participants attemptedto manage both the effect of a GD experience as well as the potential of its occurrencein the future. Participants used these behavioural responses to protect themselves andfamily from GD and, to preserve financial and social opportunities. Although differentialtreatment may present as positive (advantageous, e.g., increased support) or negative(disadvantageous) treatment (Treloar et al., 2004), strategies were used to manage theeffects or potential of a negative GD experience. We noted that participants’ behaviouralresponses or ‘strategies’ varied along two dimensions: the level of engagement with GDand the nature of the GD experience (actual experience or concern for its potential).Participants’ level of engagement with GD was reflected in the way they dealtwith the potential for or experience of GD and varied from high to low levels. Individuals88who were highly engaged with GD formed an understanding of it and factored it into theirown as well as their families’ lives. Engaged participants acknowledged the relevance ofGD and directly attended to its potential or experience in an active fashion. In contrast,participants who engaged with GD to a lesser extent did not directly attend to GD andmanaged its potential or experience in a reserved or limited way. For example,participants did not reflect upon the experience, nor made strong connections betweentheir experiences and GD (Bombard et al., 2007a).The nature of the GD experience, that is, whether individuals were managingactual experiences of GD or concerns related to the potential for GD, also influenced thetype of strategies used. Those who were concerned about the potential of GD includedparticipants who never experienced GD as well as those who had a GD experience andwanted to manage the future occurrence of another GD event. Participants wereconcerned about the potential of GD in various contexts including their workplace,insurance, health care, family and social relationships. There were varying degrees ofconcern for themselves and their family members. In contrast, participants that had anactual experience of GD responded in ways to manage the effect of that experience. (Itis important to note, however, that references to the participants’ experiences of GD arebased on their perception of the event that occurred. Thus, no distinctions have beendrawn between their perceptions and actual experiences of GD.)Depending on participants’ level of engagement with and experience of GD, fourdiscernable strategies to manage GD were reflected in their accounts: “keeping low”,minimizing GD, preempting GD and confronting GD (See Figure 1). Although a certainstrategy was dominant for each individual in a particular context, strategies varied acrosstime and context and depended on the number of concerns or GD experiences.“KEEPING Low”“Keeping low” was the strategy used to manage GD by individuals who displayeda low level of engagement with GD and were concerned about its potential. Thisbehavioural strategy involved attempts to pass or carry on as though they did not have astigmatizing identity due to their genetic test results. Overall, 23 participants (62%)described using this strategy.Keeping private about one’s family history or genetic test results was apredominant feature of this strategy. Participants kept private about their risk to varyingdegrees. Some participants spoke about not “sharing the information” at all or only with a“very limited” group of people. This group typically included family and close friends,89described as the “inner circle.” Others approached their predictive test results in aprotective or “cautious” fashion, concealing their genetic test results more than theirfamily history. Ben (pseudonyms have been used to protect the identity of participants),a participant in his thirties, explained:I’m a bit more careful now I think, just I don’t really tell many people I’ve testedpositive. Whereas I might have told them that there was this family history ofHuntington’s, I probably did tell a few friends about that. But I think now that theresult was positive I haven’t told many people.Many participants who “kept low” by deliberately keeping their test results privatereasoned that such information was “unnecessanj’ or “none of their [others/employers’]business.” The distinction between “having a gene and diagnosis” was a particularlyimportant point for some participants. Prior to diagnosis, they are healthy and did not feelthat this information was relevant. Moreover, participants explained that since thedisease is the “way it is” with an undefined time of symptom onset they may perceivedas ‘crying wolf’ by disclosing their predictive test results. Wesley, a corporate executive,described his decision to keep private as a “struggle” as he explained,I struggled a lot.... I thought about if, you know, taking on a new role, taking on anew job which I’ve just recently done, is not something I should do, it’s notsomething I should tell somebody about, you know, should I tell somebody that Ihave this condition that in five years time might affect me and all of that and Isaid, you know what: “no.”Those who worried about the possibility that disclosure of their genetic test resultmay lead to “judgment’ did not want to have people wondering about their jobperformance. Rachel, involved in middle management, did not want to give her coworkers or employers “a chance” to treat her negatively, a sentiment shared by others.Another participant perceived the notion of disclosure as “ludicrous” conveying thestrong endorsement for this strategy which was shared by other participants. In contrast,others spoke of this strategy as a “preference.” Some participants employed this strategyin a default fashion, rather than a predetermined plan. These participants suggested thattheir genetic test results simply “never came up” or “never been an issue.”“Keeping loW’ was also reflected in actions related to avoiding changes inemployment or insurance arrangements. Individuals explained that they stayed in theirjob in order to avoid the potential loss of insurance benefits, while others did not botherapplying for insurance because they were convinced that they would not qualify and thusavoided the probable rejection. Participants also found it important to “keep low”90because of the inherent connection between employment and insurance contexts; wheredisclosure in one area may lead to disclosure in the other. Also, laying low wasperceived to be necessary when some participants were concerned about GD inunknown contexts. Hugh, a father of three, explained the nature of his concerns for hischildren in a variety of contexts,I mean... [GD can occur in] any context that they [children] operate in, I suppose,might be potentially one that they could be treated differently in. As I say they goto school and they go to work and they have their friends and social settings andyou know potentially even family settings, I suppose...Some participants also kept low because they perceived their HD risk status assomething potentially stigmatizing. A few participants spoke of their HD risk status as “inthe closet”, a notion typically associated with stigma and shame. Charles, a marriedfather of two, perceived his HD status as potentially stigmatizing for his children when heasserted: “There’s enough bias out there based on [one’s] religion and race, they [hischildren] don’t need anything else to jump into the picture.” Thus he kept “it tight’because of the perceived sensitivity of the information.Some individuals conceivably used this strategy as a general coping oravoidance mechanism. Upon reflecting on disclosing her HD status to others, Kate, aparticipant in her twenties, exclaimed: “Oh god.... I would have to explain the wholesituation over and over again.. ..it was tough going through it and tough dealing with theanswer when I got it.” Keeping low may be considered as a strategy to cope with the testresults in general.The level of familiarity and trust with another person or contact was an importantfactor in determining how individuals kept low. For example, Rachel recognized that shedisclosed her HD status to her old boss because he “was a friend’ whereas her currentboss was not and could not be trusted to refrain from using the information in the “wrongway.” Level of familiarity and trust were perceived to be important factors in howparticipants kept low.MINIMIZING GDMinimizing GD characterized the behavioural strategy of participants that hadexperienced GD and had low levels of engagement with GD. Typically, participantsusing this strategy did not reflect upon the experience, nor made strong connectionsbetween their experiences and GD. Moreover, some participants were ambivalent aboutwhether particular experiences constituted GD. In these circumstances, individuals91screened out the incident (s), in effect minimized the GD experience. This strategy ofminimizing GD included: backing off, avoiding confrontation and disregarding a GDencounter. Overall, 11 participants (30%) discussed using this strategy.Many participants discussed backing off from a GD situation, essentially notpursing the incident further. Individuals “backed off’ from legal proceedings where theirtest results were used against them, others “backed down” when early retirement wasimposed on them due to their test results. Patricia, involved in administration, explainedher reaction to her employer’s demand for her early retirement to minimize their longterm disability policy costs: “I have to retire at my earliest retirement date so that’s theonly, you know, thing that has been imposed to me is that so, you know, I think that Ihave backed down.”Although backing off may be considered as shying away from a situation andavoiding confrontation, some participants perceived the use of this strategy as importantin maintaining relationships. For example, Rachel discussed her preference of notexpressing her discomfort with her mother’s change in communication patterns with herfollowing notification of her genetic test results. She explained, “I don’t want to address itwith her [mother].... I didn’t want to bring it up.... I don’t want to make her feel like she’sgetting any kind of pressure from me.” Backing off included resignation and anacceptance of GD. Kate shrugged off the suggestion of re-applying for insurance afterbeing denied when she retorted: “Why go through that if you’re going to get deniedagain.” She reconciled the experience by concluding she did not need insurance.Participants reasoned that minimizing GD allowed them to move on with theirlives. Patricia explained this approach: “It will have to, you know, be like water on theduck’s back, you just ignore it [GD] and do the best you can with it.” Participants alsodiscussed how they “blow off’ discriminatory incidents claiming: “It doesn’t matter.” Beth,a participant in her forties, expressed this sentiment after considering challenging herinsurance denial: “Then I thought what’s the point, it would just be long, drawn out . . .it[confronting GD] would be a waste of my time and my effort.”Minimizing GD was also a strategy used by individuals who thought theyunderstood the reason behind the discrimination. Upon reflecting on her experience of aretirement date being imposed on her, Patricia said:I understand that because... I don’t think that I should be able to use the long termdisability benefits until I’m sixty-five. I think that would be wasting the long termbenefits. I can get my pension next year although it’s going to be less than what I92would normally get but I can understand why they [employers] wouldn’t want me tobe on long term disability for a long period of time.In other instances, participants covered or minimized the significance of their GDexperience by constructing GD as “logical’ or “just business”. Elle, a mother of two,maintained that being charged an additional premium for her insurance “wasn’t huge.”Participants appeared to minimize the consequences of GD in order to reduce thetension or emotional reaction caused by the experience of GD.Sometimes participants chose to disregard or defer dealing with their GDexperiences in order to focus their attention elsewhere. Danielle, a single mother,discussed going through a difficult period in her life when her boyfriend “dumped” herafter she tested positive for HD. Her response to this experience was “whatever”because at the time of this incident she was helping her best friend through a cancerdiagnosis and also chose to minimize the importance of their relationship. Thus,individuals may minimize GD when they are distracted or required to manage other,more pressing issues. Similar to ‘keeping low’, minimizing GD may also be consideredan avoidant coping response to a difficult or potentially damaging GD event.Participants also minimized the experience of GD when they found other meansto get what they were after. For example, Beth thought “what’s the point” of confrontingthe insurance discrimination since she managed to secure life insurance through a grouppolicy, but admitted, “It would have been maybe different ff1 hadn’t been able to get lifeinsurance, period.” Kate, who was denied life insurance, also felt “it’s not the biggestdeal in the world” since she was covered by her work benefits. In addition, whenparticipants anticipated discriminatory outcome they readily minimized its occurrence.Kate minimized her insurance rejection but also spoke of expecting her insurance denialbeforehand. She said, “Well I was expecting it, you know.. .At the same token it doesn’tfeel too good but I had the notion that they would, that it was more of a 95% no than the5% possibility that it would be a yes.”PREEMPTING GDPreempting GD was a behavioural strategy used by participants who were highlyengaged with GD and concerned about the potential for GD for themselves and theirfamily. Preempting GD involved taking action to evade or “protect” themselves from GD.Individuals cited concern for the lack of legal safeguards for GD in Canada as a reasonfor this approach. Zara, a participant in her forties, explained: “In Canada there’s no real93laws yet developed about it [GD]... [so] there’s some concern .... Until some laws are inplace or something .. . why take a chance.”An important feature of preempting GD was taking initiative in an open and directfashion to reduce the potential for GD. The following measures characterized thisstrategy: purchasing life insurance prior to predictive testing, educating the public aboutHD, and ensuring one’s predictive test results were not listed in their GP’s medical files.A predominant example of preempting GD was purchasing insurance beforeundergoing predictive testing or prior to a family member’s official HD diagnosis, astrategy frequently encouraged by genetic professionals. In this way individuals mayqualify for insurance based on their family histories so that the principle of good faithmay be upheld, since applicants have an obligation to disclose any relevant informationat the time of application otherwise they risk having their contract annulled. This strategywas described as “slipping through” the insurance system in order to have a “safety net.”Similarly, participants spoke of extending this “safety net” to their children. Wesley, amarried father of three, proposed purchasing insurance for his children to “protect” themfrom GD.One of the things I can do for them [children] before they have any [genetic] testingdone or anything like that is to perhaps buy them some insurance policies.., becauseonce you have the insurance it’s easier to keep it.... Just have them [children] do themedicals and so then at least they have something with base protection.Some participants instructed their children to obtain insurance benefits through theirworkplace and avoid predictive testing until they’ve secured insurance.Educating the public about HD was another method of preempting GD.Participants described talking to others about HD in an effort to reverse their perceptionsof a general lack of awareness of HD in the public, referred to as the “ignorance factor”.They took it upon themselves to provide factual information on HD whenever possible.Usually this interaction was less personal because the participants did not explicitlymention details about themselves. In this respect, preempting GD was a generaleducational campaign about HD and at times included an explanation of the availabilityand implications of predictive testing. In more intimate environments, educatingindividual contacts with whom participants shared their test results was a subjective andpersonal educational process, with the intention of avoiding a specific, personalencounter with GD. Rachel described her form of educating others as “giving” her friendsa “little lecture on it [HD]” so as to avoid being “treated differently.” In a related approach94Wendy, a single woman in her fifties, discussed disclosing her test results“fairly early” inromantic relationships to avoid the potential for “adverse reaction” later.Participants also took measures to ensure that their predictive test results werenot listed in their medical files by instructing their geneticists not to send medical lettersto their GPs. Some participants did this to minimize the chance that insurancecompanies discover their predictive test results if they applied for insurance in the future.Rachel said,What concerns me if an insurance company says that they want to look through themedical records and they find this [genetic test result], are they now goingto say:“No, we’re not going to cover you”?... I don’t want anything on my medical file thatsays that’s a positive result because I believe that insurance companies would treatme differently knowing that even though I’m not symptomatic.Others were concerned that they could be treated differently by physicians when theyare diagnosed with HD in the future. Participants also encouraged othersto preemptGD. Zara told her nephew, “Go back to your doctor and tell him to take it [test results]out of the [medical] file, keep it out of there.”Financial circumstances were also taken into account. Those in higher socioeconomic positions were less concerned about preempting insurance and employmentdiscrimination. Wesley alluded to this after he discussed his plan to purchase lifeinsurance for his children,But again financially I’m not too worried because unless we have a huge stockmarket wreck or a big crash or something, I can help them [children], you know, ifthey get into a situation where, you know, this affects their ability toget insuranceor whatever, you know, I can help them.CONFRONTING GDUnlike highly engaged participants who were concerned about the potential forGD, those who were highly engaged with GD and had an encounter with GD confrontedit head on, resisting or challenging the GD experience. Confronting GD wascharacterized by a spectrum of approaches including: challenging the perpetrator,seeking advice, and refuting the basis for discrimination.In responding to differential treatment such as judgmental comments participantsdiscussed confronting their perpetrators by “making others listen” and telling others thatthey “don’t want to be treated that way.” An experience with GD seemed to empowersome to confront further discriminatory experiences. Whistle blowing became a strategyof choice for those with multiple GD experiences. Michelle, a healthcare professional,95considered her HD test result as an “ace card’ for exposing GD. Her boss requestedaccess to her medical files for surveillance purposes after discovering her genetic testresults. Although Michelle refused this request, she believed she retained the upperhand:I hold the ace card basically because, if they, if I feel I am being shafted inanyway I can pull out the ace card and say prejudice.... If I apply for a positionand I feel that, you know, they’ve declined me because of Huntington’s... if I feelthat in any way I would have no qualms about going to the Times columnist andgoing hey you know... this is what’s happened.Participants also sought the advice of legal experts, protection of unions, andsupport of friends and trusted health care providers in confronting GD. Oliver, aparticipant involved in public transit who had been recently fired at the time of theinterview, sought assistance from his union in dealing with conspiracy he perceivedoccurred among his physicians and a driving instructor which culminated in hisdismissal. Others, who wanted to confront uncomfortable behavioural andcommunication changes in their family related to GD, sought the support of health careprofessionals, such as psychologists. After learning of his test results, Wesley recalled:“She [wife] began to evaluate me through a different lens and she was seeing changesin me that I wasn’t seeing.” He worried that this treatment impacted their relationship. Heencouraged his partner to attend joint counseling sessions “for the sake of therelationship.”Some participants complained of being “shunned” or were treated as though theyhad a “contagious disease.” When they faced a discriminatory situation someindividuals attempted to refute the basis for the differential treatment. They wouldattempt to explain the distinction between having a gene mutation and having a diseasewhile others would explain to others that they are not currently sick. Beth described herfriends’ treatment of her after she told them of her genetic test results:At first they treated me like I was made of glass, like I was going to break andthat lasted for about a month.... [They were] just very-very careful in what theysaid and how they said it. I mean you could tell the effort was there but theywere being very-very careful and everything they said and everything they did soit wouldn’t upset me. And that just drove me nuts. And I just looked at them and Isaid, “I’m not sick” “I’m not dying” I said, “Sure I have this thing but I’m fine”.Individuals’ tolerance for ambiguous or awkward situations determined how theyconfronted GD. Beth discussed her lack of tolerance for the “shunning” and thus96frequently confronted individuals that “have a problem”with her. These personality traitsin addition to being generally “strong and stubborn” individualswere perceived to beimportant factors in how participants confronted GD experiences.4.4 Discussioi’iThe results of this study suggest four broad strategies are used to deal withgenetic discrimination: “keeping low”, minimizing, preemptingand confronting geneticdiscrimination. This typology is presumed to be specific for asymptomatic individualscoping with a potentially discreditable identity as a consequence of beingat increasedrisk for a late onset genetic disease. Given the recentattention surrounding geneticdiscrimination (Apse et al., 2004; Lapham et al., 1996; Peters et al., 2005), learninghowindividuals deal with real or potential genetic discrimination is of importanceto geneticsprofessionals in assisting individuals effectively mange these issues. Thus, thesestrategies may provide a framework for understanding howother individuals managegenetic discrimination for other genetic diseases for which predictive testing is available.These include breast and colons cancers, and other neurologicaland cardiovascularconditions such as spinocerebelar ataxias, myotonic and musculardystrophies,Alzheimer’s disease, thrombophilia, hypertrophic cardiomyopathy andMarfanSyndrome. These findings may prove particularly relevant forcancer genetics settingswhere calls for new approaches to address genetic discrimination duringgeneticcounseling have been recommended (Kausmeyer et al., 2006).Research attention has recently focused on the stigmatization and discriminationagainst asymptomatic individuals at risk for various genetic diseases (Apseet al., 2004;Geller et aL, 1996; Lapham et al., 1996; Peters et al., 2005). The stigma-relatedcopingliterature provides a basis for understanding the results of thisstudy. Stigma can be asource of stress for stigmatized individuals (Miller and Major, 2000), and tocope with it,individuals employ strategies that are aimed at controlling and modifyingthe situation byusing psychological, social, behavioural, economic or educational approaches(Compaset al., 2001). Similarly, individuals found to have the HD expansion use predominantlybehavioural strategies to manage the experience of GD and to control itspotential.Although our typology attempts to group responses into clearly defined categories,therecan be overlap between categories, especially in different contextsand situations.Consequently, different strategies may be employed by any one person at differenttimesand across various contexts. Individuals’ use of different strategies depended on their97level of engagement with GD and on the type of discrimination experience (actual orconcern for the potential of GD).The conceptualization of engagement as an underlying dimension in explaininghow individuals manage the risk and experience of GD is supported by recent studies inrelation to coping with stigma-related stress and genetic risk for HD (Crocker et al.,1998; Lazarus and Folkman, 1984; Taylor, 2005a). Responding to stigma alwaysinvolves cognitive appraisals about the seriousness and relevance of the threat (Lazarusand Folkman, 1984). Moreover, the perception of threat is likely to occur only amongstigmatized people who self-identify with the stigma (Crocker et al., 1998). Our findingssupport these models since a GD strategy is employed as a consequence of theindividual’s perception that the threat of GD is relevant to them and that they havesomething personal at stake. In other words, one must be engaged with GD in order toperceive GD as a threat and consequently respond to it. Moreover, the nature of one’sresponse to GD will depend on their level of engagement with GD. Althoughengagement with GD is likely represented as a continuum, dichotomizing engagementwas nonetheless helpful to illustrate the different strategies individuals used to manageGD.Our results indicate that individuals who engaged with GD to a lesser extentadopted strategies of non-disclosure of their genetic test results in potentiallystigmatizing situations and stayed in unsatisfying jobs because of concerns related tohaving the HD expansion, which is consistent with previous research (Angermeyer et al.,1987; Kittikorn et al., 2006; Peters et al., 2005; Scambler and Hopkins, 1986). Theparticipants in our study divided their world into a large group to whom they tell nothing(“keeping low”) and a small group (“the inner circle”) who were informed of their geneticstatus. Medical practitioners often recommend this type of information management byinstructing patients to take caution when and with whom to discuss their test results. Theeffectiveness of such a strategy may be called into question because some stigmatheorists speculate that felt stigma (fear of discrimination) typically proves moredisruptive than enacted stigma (actual discrimination) (Scambler and Hopkins, 1986). Infact, the use of secrecy to manage social stigma has been linked to emotional distressamong caregivers of people living with AIDS (Kittikorn et al., 2006) and thus it isplausible that individuals who ‘keep low’ may experience distress. The pre-testcounseling process and informed consent includes consideration of the potentialimplications and negative effects of having predictive testing which could be considered98an attempt to encourage greater engagement with GD. However, given the potentialdistress and risk of exacerbating felt stigma inherent in this process attempts shouldbemade to temper these discussions. Given the emphasis of “keeping low” as a choicestrategy for those at risk of GD, further research is warranted in exploringtheeffectiveness of using this strategy as well as its long term impacts on emotionalwellbeing.Low levels of engagement with GD coupled with an actual experience of GDresulted in the use of strategies focused on minimizing GD among participantsin ourstudy. This approach has been previously described as a disengaged responsetodiscrimination in which participants’ choose not to reflect upon or discuss theincident(Crocker et al., 1998; Lubkin, 1986). Some participants were ambivalent aboutwhether aparticular reaction constituted discrimination. Avoidance,acceptance and minimization,elements of this strategy, have also been previously reported to be associatedwithdisengaged coping responses to discrimination (Ruggiero et al., 1997; Swimet al.,1998). Avoidance, characterized as withdrawal, resonates with the participants’desire toavoid confrontation following a GD encounter. Moreover, those who used this approachminimally engaged with GD. In fact, some research has suggested that minimalengagement is a choice strategy to cope with discrimination since individuals areable tosuccessfully reduce psychological distress and thus maintain emotional equilibriumwithout taxing their coping resources (Mogg et al., 1994; Ruggieroet al., 1997).Conversely, other evidence suggests that disengaged coping responses to stigma areless adaptive strategies to cope with stigma-related stress and may lead to adverseconsequences. For example, previous discrimination research has demonstrated thatAfrican Americans who accepted unfair treatment were more hypertensive than thosewho took some action (Krieger and Sidney, 1996). Moreover, African Americanswhoasserted that they did not experience racial discrimination were more likely to behypertensive (Krieger and Sidney, 1996). As emerging evidence suggests, individualswho chose low engagement strategies may experience less distress yet perhaps at theexpense of their physical well-being. Further research would be requiredto establishcorrelates between low engagement strategies and psychological or physical outcomes.In contrast, those who engaged with genetic discrimination to a greaterdegreeresponded to its potential by preempting it. Adapting one’s social interaction strategiesincluded behaving in a socially skillful manner in the face of prejudice. Participants’measures of purchasing insurance policies before genetic testing and keeping test99results off their GP’s medical files may be considered as dimensions of preempting therisk of genetic discrimination and attempting to achieve their goals despite their geneticdifference. Educating the public, an important measure of preempting geneticdiscrimination, was evident as participants embraced opportunities to inform othersabout HD and in doing so attempted to change other’s negative perceptions of HD.Similar approaches have been adopted by others. For example, 51% of respondents ona survey on coping with Marfan’s disease endorsed the use of education as a strategy tocope with disease-related stigma (Peters et al., 2005). The use of preemptive strategiesmay be likened to “passing,” an important response described by Goffman (1963) inwhich individuals act as if they have a less stigmatic identity or even a normal one(Goffman, 1963). Although the relative effectiveness of preempting GD is unknown, ourresults suggest that this strategy may be employed in a range of contexts andcircumstances.Resistance has been a described as a response to stigma in which participantsspeak out or challenge rules or the stigma (Dudley J, 1983). Similar to our results, someindividuals experiencing GD confronted the incident by challenging the person orinstitution responsible, seeking professional advice and refuting the basis for GD. Theseengaged strategies are characterized by a “fight” motivation (Compas et al., 2001) andan attempt to change these circumstances. Our findings suggest that participants whoconfronted GD did so in certain contexts (e.g. social and family settings) and werelargely individuals with a low tolerance for ambiguity.There are several caveats in the interpretation of this study. First, participantswere recruited from a larger observational study of individuals who underwent predictivetesting for HD. This recruitment strategy may have biased the findings because theparticipants may be considered a self-selected group (Codori et al., 1994). In addition,our study primarily explored behavioural responses to the potential or experience of GD.The array of responses to stigma is vast, including emotional, cognitive, andphysiological responses which can occur both voluntarily and involuntarily.Consideration of the diversity of coping responses may be necessary to gain a completeunderstanding of the consequences of GD. The interpretations and typology is thustentative and we are unable to immediately generalize to a larger population. Additionalresearch is warranted to explore the predictors and outcomes of using these strategiesin a more broadly representative sample. These insights would be helpful to predict the100variation in approaches and reactions to GD among individuals found to have the HDexpansion.The results of this study have implications for the care of asymptomaticindividuals living with a positive test result for HD. Genetic discrimination can bedetrimental to one’s well-being. Genetics professionals can assist their patients toanticipate struggles and encourage the use of engaged strategies to help them manageGD. Thus in the context of genetic counseling for HD predictive testing, it is imperative toexplore patients’ experiences with stigma or GD and assess individuals’ resources tocope with GD. Furthermore, clinicians should mobilize effective engaged strategies andrefer individuals who are struggling with issues of discrimination for additional support orlegal counsel. It is through insights from stigmatized individuals that we may learn how tohelp others cope with potentially discreditable identities as a consequence of testingpositive for a late onset genetic disease.101Gender FemaleMaleParticipants with HO expansion(n=37)N %23 62.2%14 37.8%Marital Status Married/common-lawSingle/separated/divorced/widow23 62.2%14 37.8%EducationEmploymentSome college & aboveHighschool & belowEmployedUnemployed/homemaker31 83.8%6 16.2%26 70.3%11 29.7%Children Have childrenHave no children27 73.0%10 27.0%Time since Testing 0-4 years5-9 years10-14 years1 5-20 years9 24.3%16 43.2%10 27.0%2 5.4%Table 4.1 Participants’ demographic informationNature of the GD ExperienceLevel ofEngagementwith GDLowHighPotential“KeepingLow”PreemptingActualFigure 4.1 Strategies to manage genetic discrimination (GD)1024.5 REFERENCESAlmqvist,E.W., Brinkman,R.R., Wiggins,S. and Hayden,M.R. (2003). 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Predictive genetic test decisions for Huntington’s disease: Elucidating thetest/no-test dichotomy. Journal of Health Psychology 10, 597-612.Treloar, S., Taylor, S., Otlowski,M., Barlow-Stewart, K., Stranger, M., and Chenoweth, K. (2004).Methodological considerations in the study of genetic discrimination - A review. CommunityGenetics 7, 161-168.Visintainer,C.L., Matthias-Hagen,V., and Nance,M. (2001). Anonymous predictive testing forHuntington’s disease in the United States. Genet. Test. 5.Williams,J.K., Schutte,D.L., Evers,C.A., and Forcucci,C. (1999). Adults seeking presymptomaticgene testing for Huntington disease. Image J. Nurs. Sch 31, 109-114.106Chapter 5: The Extent of Genetic Discrimination1A version of this chapter will be submitted for publication as:Yvonne Bombard, Lauren Curry, Gerry Veenstra, Susan Creighton, Jan Friedman, Jane S. Paulsen, Joan L.Bottorif and Michael R. Hayden on behalf of the Canadian Respond-HD collaborative researchgroup*.Family history, rather than genetic test results, is the major reason for experiences of genetic discriminationamong persons at risk for Huntington disease.*Canadian Respond-HD collaborative research group are:Mark Guttman & Christine Giambattista, Centre for Movement DisordersMark Ludman, Jill Murphy & Tina Babineau-Sturk, IWK Health Centre.Patrick MacLeod & Jennifer Rice, Victoria General HospitalWayne Martin & Marguerite Wieler, University of AlbertaWendy Meschino & Clare Gibbons, North York General HospitalLynn Raymond & Joji Decolongon, University of British ColumbiaOksana Suchowersky & Mary-Lou Klimek, University of Calgary1075.1 INTRODUCTIONThe completion of the Human Genome and HapMap Projects along withaccelerating advances in genomics has heralded a revolution in genetic medicine.Genetic medicine offers many diagnostic,. treatment and reproductive options that caninform decision-making and relieve uncertainty. However, these powerful newtechnologies have also produced significant fear for the potential misuse of geneticinformation to discriminate against healthy individuals on the basis of geneticpredisposition for a disease (Apse et al., 2004; Hall et al., 2005).Indeed fear of genetic discrimination (GD) is widespread and has preventedindividuals from undergoing genetic testing (Apse et al., 2004; Peterson et al., 2002) andparticipating in genetic research (Hadley et al., 2003), thereby hindering potentiallybeneficial engagement with genetic medicine and possible treatment opportunities. Inthe context of breast cancer, for example, many women at increased risk decline testingfor the BRCAI/2 susceptibility gene for fear of health insurance discrimination (Petersonet al., 2002). Statistically half of those who decline would be positive (Peterson et al.,2002) and thus deny themselves possible psychological relief, preventative managementand/or treatment opportunities due to fear of GD.Policy makers in the United States have responded with a bill to prohibit the useof genetic information in health insurance and employment decisions. The GeneticInformation Nondiscrimination Act (GINA) proposes to prohibit group and individualhealth insurers from using a person’s genetic information in determining eligibility andsetting premiums as well as requesting or requiring potential applicants to undergogenetic testing. GINA would also bar employers from using genetic test results in theirhiring, firing, job placement, or promotion decisions (Hudson, 2007). GINA has nowpassed in the House of Representatives and is currently awaiting review in the Senate.Despite significant efforts aimed at protecting individuals from the potential ofGD, it is still unclear as to the frequency and severity of GD. In fact, evidence to supportthe promulgation of this law is hampered by a paucity of evidence indicating whether GDexists and in which settings. Reports of GD have been largely anecdotal to date. Earlyreports were often third-hand, and allegations of discrimination were usually based ondisease as opposed to genetic predisposition (Apse et al., 2004; Kasset al., 2007;Lapham et al., 1996; Low et al., 1998). To date, no large-scale empirical studies have108investigated the nature and prevalence of GD in a population that is currently healthybutis predicted by genetic testing to have a very high likelihood of developing a geneticdisease.Huntington disease (HD) was the first adult-onset genetic disease for whichapredictive test was developed that allows at-risk individualsto know with near certaintywhether they inherited the causative CAG trinucleotide expansion in the HDgene(Langbehn et al., 2004; MacDonald et al., 1993). The introduction of the HD predictivetesting program has led to the advent of a new group of individuals - individualswhohave the CAG expansion and are currently healthy yet are destined todevelop thedisease should they live long enough. GD was identified asa potential risk of predictivetesting (Craufurd and Harris, 1986; Perry, 1981), yet little is known about whetherpredictive testing for HD actually results in discrimination. While discrimination onthebasis of family history has been knownto occur in the insurance context (Harper et al.,2004), the question of whether predictive testing for HD confers heightenedrisk ofdiscrimination has yet to be answered. We assessed the nature and prevalence of GDina cohort of asymptomatic genetically tested and untested individuals at risk for HD. Wealso examined whether genetic testing is associated with increased levels of GD.5.2 MethodsSTUDY POPULATIONA cross sectional survey of asymptomatic persons at risk for HD was undertaken.Seven genetics and movement disorders clinics, servicing rural and urban communitiesand representing ten of Canada’s provinces, were invited to participate. Approval oftherelevant research ethics boards was received.A total of 300 asymptomatic individuals at risk for HD were targeted in thefollowing three categories: individuals who underwent genetic testing and were foundtohave the HD mutation (HD+), individuals at 50% risk who were found not to have theHDmutation (HD-), and individuals who chose not to undergo genetic testing for HD(NotTested; NT). We chose to focus on experiences of GD based on genetic informationrather than discrimination experiences based on symptoms of HD or disability concerns.Asymptomatic individuals were identified from clinical charts using the UnifiedHuntington Disease Rating Scale (UHDRS) and recent neurological assessments. Thepopulation of interest included all individuals age 18 years from HD families who had109UHDRS scores < 2 and had not been diagnosed with signs or symptoms of HD withinthe past year.DEVELOPMENT OF THE SURVEY INSTRUMENT AND TESTINGThe study instrument was developed based on an initial qualitative study of theexperiences and concerns of GD among persons at risk for HD (Bombard et al., 2007a;Bombard et al., 2007b) and included questions adapted (with permission) from thevalidated and frequently used instruments developed by Taylor et al (Taylor et al., 2004)and Krieger et al (Krieger et al., 2005). The study instrument was validated by an expertreference group who individually critiqued the questionnaire to ensure that the itemswere relevant and consistent with GD issues experienced by persons at risk for HD.Cognitive interviews were used to test for uniformity in comprehension and comfort withquestion wording and response formats. The pretest questionnaire was mailed to 19individuals in order to test the comprehension of questions, instructions and skippatterns and pilot the data collection procedures and to ensure variability in the data.The final questionnaire included 122 questions and skip patterns suitable for the3 subgroups of our study. The sections focused on: (I) genetic status and family history(FH) of HD, (2) perceptions of genetic testing, (3) concerns and experiences of knowingabout FH, (4) concerns and experiences of knowing genetic test results (GTR), (5)specific incidents of disadvantage or unfair treatment, (6) thoughts and experiencesrelated to insurance, (7) knowledge and attitudes towards genetic issues and (8) sociodemographic information.ASSESSMENT OF FAMILY HISTORY & GENETIC STATUSRespondents were asked the following question with regard to their familyhistory: “In approximately what year did you first become aware that HD was in yourfamily?” The genetic status of the respondents was assessed using the followingquestion: “have you had a genetic test for Huntington disease?” The follow-up questionswere: “in what year did you have the genetic test?” and “did you get a positive test result(i.e. you have inherited the HD gene expansion)?” Responses to these questions formedthe basis for classifying individuals as tested, not tested, HD+ and HD-.ASSESSMENT OF EXPERIENCES OF GENETIC DISCRIMINATIONWe asked respondents whether they have ever experienced discrimination invarious situations because of their FH. To differentiate between experiences of GD110based on GTR as opposed to experiences of GD based on FH, we also asked testedrespondents whether they have ever experienced discrimination in similar situationsbased on their GTR. We operationalized discrimination as ‘being unfairly prevented fromdoing something or being treated differently’ which was the dominant interpretationprovided by participants in the qualitative study. A total of twenty-three possible contextsfor discrimination were provided to the respondents, as listed in Table 5.2. Responsecategories were yes, no and not applicable. Respondents who checked yes to anycategory were considered to have had an experience with GD. In order to identify theprevalence of GD in major settings, the 23 items were collapsed into the following subcategories: insurance, employment, social, family, government and health care, asindicated in Table 5.2.The questionnaire also included the following open-ended question to allowrespondents to describe or further elaborate on their experience(s): “Are the any clearincidents of disadvantage or unfair treatment related to your family history of HD orgenetic test results?” Quotes were selected that represented the most frequent type ofGD experience in a particular setting or that provided details of the event that occurred.ASSESSMENT OF PSYCHOLOGICAL DISTRESSPsychological distress was chosen a priori to be a primary psychologicaloutcome measure since it has been previously associated with racial, gender, sexualand ethnic discrimination (Amaro et al., 1987; Landrine et al., 1995; Meyer, 1995;Williams, 1997). Respondents nominating at least one experience of GD were asked torank the resulting level of distress they experienced on a scale of 1-5 (where I indicated‘not distressing’ and 5 indicated ‘very distressing’).DEMOGRAPHIC INFORMATIONRespondents were asked to report their age, marital status, employment status,whether they had children, the highest grade or level of education attained, culturalbackground, income level, the type(s) of insurance purchased and which of their parentshad HD and their age of onset.ADMINISTRATION OF THE SURVEYThe questionnaires were administered during individuals’ annual scheduled clinicappointments or by mail between June and December 2006. Using the Dillman tailoreddesign survey method (Dillman, 2000), postal respondents were mailed the111questionnaire, a personalized introductory letter, a postage-paid return envelope and a$25 honorarium by health professionals at each clinic. Approximately one week after theinitial mailing all postal respondents were sent a reminder/thank you postcard. A secondset of survey materials was sent to non-respondents four weeks after the initial mailing.Additional telephone contact was made with non-respondents after five weeks. Writtenconsent was obtained from all respondents.STATISTICAL ANALYSISDescriptive statistics are reported for the experiences and prevalence of GD. Theprevalence of GD is reported in three dimensions: GD based on FH, GD based on GTRand overall (i.e. we made no distinction between FH and GTR; those who reported anexperience of GD based on either or both FH and GD were counted once). The Fisher’sexact test and Pearson’s chi-squared tests of significance were used to investigatebaseline demographic differences between the study groups (tested (HD+ & HD-), not-tested (NT), HD+, HD- & NT) as well as differences between the study groups andsettings among respondents reporting experiences of GD. Comparisons of means wereconducted using Mann-Whitney U and Kruskal Wallis tests1.Logistic regression analysiswas used to develop a model to predict the likelihood of experiencing GD. Threeregression models were developed: (1) unadjusted: where all variables were entered inthe model individually, (2) adjusted for age, and (3) adjusted for all demographic factors.All analyses were conducted using the statistical software package SPSS version 11.5.Significance tests were two-tailed and alpha was set to 0.05. The false discoveryrate (FDR) procedure was used for multiple comparisons in our exploratory analyses(sub-analyses of differences in GD between groups within the various settings, giventhat there are over 42 comparisons). Since fewer comparisons were being made in ourhypothesis-driven analyses (overall differences in GD between tested versus untestedrespondents, HD+, HD- & NT, i.e., 4 comparisons), no procedure to correct for multiplecomparisons was deemed necessary.1Non-parametric tests were used since the sample size was relatively small and the parametersof the variables of interest were unknown.1125.3 ResultsCHARACTERISTICS OF THE RESPONDENTSOf the 299 individuals invited to participate in the survey, 239 individuals returneda completed questionnaire, representing an overall response rate of 80%. Six surveyswere excluded from analyses since these individuals were found to have UHDRS scores>2at some point after consenting to join the study but before completing the surveyquestionnaire, rendering an adjusted response rate of 79.5% (233/293). Characteristicsof the remaining 233 asymptomatic respondents are presented in Table 5.1. Nosignificant differences in baseline characteristics were detected between the studygroups. Furthermore, there were no significant differences between the responders andnon-responders with respect to gender (P =0.206), age (P =0.077), test status (P=0.334) and gene status (P 0.365). Socio-demographic characteristics of our sampleappear similar to those of other HD populations in North America (Almqvistet al., 2003;Babul et al., 1993; Codori and Brandt, 1994; Quaid and Morris, 1993; Wiggins et al.,1992) and the Netherlands (van, I et al., 1994) as well as several other geneticpopulations (Apse et al., 2004; Armstrong et al., 2003; Hall et al., 2005; Kass et al.,2007) with the general exception that our sample is older and more educated.NATURE AND EXTENT OF GENETIC DISCRIMINATIONTable 2 shows that genetic discrimination was reported by 39.9% (n=93) of thesample. Discrimination experiences were most prevalent in insurance (n=68, 29.3%),family (n=36, 15.5%) and social (n=29; 12.6%) settings, with discrimination inemployment, health care and government settings reported less frequently as shown inTable 3.In the insurance setting, discrimination occurred most often in relation to lifeinsurance (n=63, 27%) and long-term disability insurance (n=49, 21%). Seventyrespondents (30.0%) completed the open-ended area of the questionnaire, elaborating113on their experiences2.Some respondents offered the following descriptions of theirinsurance-related experiences: “I was so angry because I was told I was denied [lifeinsurance] because of my gene”, “[I was] refused coverage for life insurance due to [my]family history. They wanted me to take the test and find out the results to determine ifthey would give me coverage”, “insurer agreed to provide insurance but at a rate over 10times higher then the normal because of the family history of HD. . .at the time [I] did notreceive genetic testing”.In the family domain discrimination occurred most often in reference to makingreproductive decisions (n=27, 11.6%) and experiences with family members (n1 5,6.4%). Respondents explained: “[My] mother and brother [were] insisting [that] I gettested when I was pregnant [saying] it was my responsibility’, “[A] family relative voicedher opinion that I might not want to complete a master’s degree given I had testedpositive for HD.”Within their social circles, some respondents believed they were sometimestreated unfairly by their friends (n=18, 7.7%) and when establishing relationships (n=14,6.0%). A respondent mentioned “basically [boyfriend] dumped me [after testingpositive].” In health care, most discrimination was reported to occur when gettingmedical care (n=1 1, 4.7%), by doctors (n=8, 3.4%) and by other health careprofessionals (n=7, 3.0%). One respondent shared that “[my] doctor recommended nothaving children when Father’s diagnosis was disclosed that he had HD.”There were few reports of GD within employment settings (6.9% overall). Whenreported, GD occurred most often at work (n15, 6.4%) as opposed to gaining access tojobs n7, 3.0%). One man explained: “I disclosed my positive result to my employer. [I]was denied a promotion, in large part, because of the perceived future liability to thecompany.” Another tested woman described her experience prior to her genetic testing:“I was denied an opportunity to interview for a more senior position in my present place2Respondents offered descriptions of GD experiences related to most settings; however, themajority of descriptions involved insurance (n=36), family (n=11) and employment (n9).Experiences related to health-care (n=8), social (n=3) and government (n=2) were offered lessfrequently. One respondent’s description was not clear and thus was not categorized.114of employment, despite that I had the necessary skills, knowledge, and experience. Themanager responsible for hiring for the position told me they thought that I was notinterested in upward professional mobility and that my greater focus was on having amore well rounded life, that the job was a more demanding one than I wanted - despitethe fact that I applied for the job and thought that to be a clear indicator of my interest init.”In government settings, discrimination was reported infrequently (3.9%) but whenreported it occurred most often in reference to getting access to or custody of children(n=5, 2.1%), in the law courts (n=4, 1.7%) and during adoption (n=3, 1.3%). Thefollowing tested respondent offered her experience prior to undergoing genetic testing:“We had already been approved and were waiting to adopt when my mother wasdiagnosed with HD. All of a sudden, [we were] no longer considered a viable couple.[We were] told [we] could adopt a special needs child but not a healthy baby.”GENETIC STATUS AND GENETIC DISCRIMINATIONAs table 5.3 shows the proportion of respondents who experienced GD was atleast 16% higher in the HD÷ group than in the HD-(X2P=0.042) and NT(2P=0.045)groups. This suggests that respondents who test positive for HD are the most likely toreport experiences of GD. Interestingly, there were no significant differences in theproportions of GD experiences between HD- and NT respondents (n=29184; 34.5% vs.n22/66; 33.3%,x2P =1.00), suggesting that testing negative for HD may notnecessarily decrease the likelihood of experiencing GD (a possible explanation is offeredbelow).Trends across most of the settings and groups suggest that reports of GD byHD+ respondents were up to 11.2% higher than in the HD- group and up to 15.3%higher than in the NT group (Table 3). In fact, compared to NT respondents, reports ofGD by HD+ respondents were 15.3% higher in the family setting(x2P0.013), 14.4%higher in social settings(x2P0.016) and 12.9% higher in employment settings(x2P=0.007) (P-values did not reach the required FDR-adjusted significance levels ofP0.007, 0.011 and 0.005, respectively). Moreover, within the employment setting, HD+respondents also reported 10.9% more experiences of GD than HD- respondents(x2P=0.016 — above the required level of significance of P0.01 0).When comparing discrimination experiences between the tested (i.e. HD+ & HD-)and NT groups, the proportion of respondents who experienced GD was 9.2% higher in115the tested group (n=71 vs. 22,x2P =0.236; Table 3). Although this difference is notsignificant at the group level, trends across most of the settings indicate that testedrespondents experienced 5 -11% more GD than did NT respondents. Specifically, in thefamily and employment settings, tested respondents reported 7.5 and 11% more GDthan those who did not test (family: n=31 vs 5[X2P=0.044] and employment: n=15 vs. I[x2P = 0.045]. However, after adjusting for multiple comparisons, these differences werenot statistically significant (the required levels of significance were P0.014 andP0.01 5, respectively).In summary, while participating in genetic testing itself is not significantlyassociated with discrimination, testing positive for HD is associated with an increasedlikelihood of reporting discriminatory experiences that tend to occur mostly in family,social and employment settings.REPORTED REASONS FOR GENETIC DISCRIMINATIONRespondents’ family histories (FH) rather than their genetic test results (GTR)were reported as the major reason for GD. Among the 71 tested respondents whoreported at least one experience of GD, 41 individuals attributed their experience(s) totheir FH while 13 of the respondents believed that their GTR was the major reason fortheir discriminatory experiences. Seventeen tested respondents (17/71; 24%) attributedtheir experiences to both FH and GTR3.Attribution differences varied between the HD÷ and HD- groups. Among 29 HDrespondents, two respondents attributed their GD experiences to both their FH andGTR, 26 respondents attributed their discriminatory experiences to their FH alone whileone individual ascribed the experience to her test results only. This woman reported GDamong her siblings, noting that “they were envious”.Statistically significant differences in proportions between experiences of GD based on FHversus GTR were not assessed since non-parametric tests on paired samples, such as theMcNemar’s test of marginal homogeneity, do not take into account the respondents who choseboth FH & GTR which represent an important category of responses.116Attribution differences were less evident among the 42 HD+ respondents. FifteenHD+ respondents attributed their GD experiences to both their FH and GTR. Amongthe27 respondents who distinguished between the bases of their experience(s),15individuals believed they were discriminated against because of their FH and 12 othersconsidered their GTR to be the primary reason for their GD experience(s). It is notablethat a large proportion of the HD+ respondents (n=15) attributed their GD experiencestotheir GTR and FH.PREDICTORS OF GENETIC DISCRIMINATIONThe results of the regression models predicting GD are reported in Table 4. Themodels have an overall R squared of 0.064, 0.083 and 0.204, respectively. Individualswho reported first-hand experience with HD, were aware of their FH at a youngerageand knew about their FH for over 15 years were at greater risk of experiencingGD(Table 4). Individuals who had known people with HD symptoms or who have died fromHD were more likely to report GD (OR = 3.36, P0.01). Respondents who have knownabout their FH for 15 years or more also were more likely to report GD (OR = 2.63,P=O.005). Older individuals were less likely to experience GD (OR = 0.95, P=0.004).While a significant association existed between having a college/university degree andexperiencing GD (OR = 2.03, P=0.038), this relationship was not significant afteradjusting for socio-demographic factors.The odds of experiencing GD were 3.39-3.55 times as high for respondents whobecame aware of their FH before age 34 compared with those who learned about itwhen they were over 35 years old (P=0.016). The majority of GD among those wholearned about their FH at a young age occurred in reference to insurance(x2P0.005),in the family(x2P=0.033) and in the health care setting(x2P=0.006).PSYCHOLOGICAL DISTRESS AND GENETIC DISCRIMINATIONPsychological distress was found to be associated with the experience of GD(X2:relationship between distress and GD based on FH: P0.0001 and GD based on GTR:117P=0.01j4)Experiencing GD in more situations based on FH and GTR was associatedwith increased levels of distress (Pearson R 0.384 and 0.526, P0.0001, respectively).Among those who attributed their experiences of GD to FH only, the mean levelof distress was 3.57 (n=63 [tested n=41, NT n=22], SD=1 .28). Levels of distress relatedto GD based on FH did not differ between the tested and NT groups (tested mean=3.51vs. NT mean=3.68, Mann-Whitney U P=0.480) nor between all three groups (HD+=3.00,HD-=3.81, NT=3.68, Kruskal Wallis P—0.121).Among those who attributed their experiences of GD to GTR only, the mean levelof distress related to GD based on GTR was 2.85 (n=13, SD=1.56). Distress levels didnot significantly differ between HD+ and HD- respondents (HD+2.92 vs. HD-2.00,Mann-Whitney U P=0.769).Among those who attributed their experiences of GD to both FH and GTR, themean level of distress was 3.65 (n=17, SD=1.32). Interestingly, levels of distress did notdiffer significantly between perceived causes of GD (FH vs GTR vs both, Mann-WhitneyU P>0.05) or genetic status (Mann-Whitney U P=0.721).5.4 DiscussionThis is the first study to report the nature and prevalence of GD amongasymptomatic individuals who have participated in genetic testing in comparison toindividuals who chose not to be tested. Discrimination was reported by 40% of thesample and occurred most often in reference to life and disability insurance, makingreproductive decisions, friends and establishing relationships. Testing positive for HDwas associated with increased experiences of GD. FH appears to be a major reason forand predictor of experiences of GD. Those who discover their FH at a younger age andknow of their FH for longer are also at greater risk for GD. Our results demonstrate thatGD is a significant social issue and source of distress for persons at-risk for HD.These results raise important ethical, legal and social issues regarding geneticinformation and the consequences of genetic testing. Clearly, reports of discriminationDue to the small sample sizes, ranks 1-3 and 4-5 were collapsed to represent low-moderate andhigh levels of distress118experiences were relatively common among persons at-risk for HD with forty percent ofthe respondents reporting at least one experience of GD. Nearly one in threerespondents experienced insurance discrimination, largely by life and disabilityinsurance companies in the forms of insurance rejection, premium increases or requeststo take a predictive test. Discrimination by insurance is a significant concern amongvarious at-risk populations (Apse et al., 2004; Hall et al., 2005; Peterson et al., 2002)and studies have shown that genetic populations are at greater risk for insurance GDcompared to both the general population (Low et al., 1998) and those with commondisorders (Kass et al., 2007). However, our results do not support such trends as geneticstatus was not associated with increased levels of GD in the insurance settings. It hasbeen documented that individuals at-risk for HD employ various strategies to manageGD (Bombard et al., 2007b), thus it is plausible that these findings support the notionthat individuals may be preempting GD by purchasing insurance prior to undergoinggenetic testing.Surprisingly, family and social circles were the next major sources ofdiscriminatory experiences. Twelve - fifteen percent of the respondents reported GD inthese settings, mostly with regards to reproductive decision making, by relatives andfriends and when establishing relationships. No survey to date has exploreddiscrimination in areas other than insurance and employment; and our results are thefirst to report experiences of discrimination in the family context. However, discriminationin the family must be viewed through a wider lens that captures the profound impact thepresence of HD has on the family system. Often when HD is known to be present in afamily it becomes part of that family’s identity and patterns of behaviour. Genetic testinghas also been shown to have profound impact on family functioning (Sobel and Cowan,2000). As others have aptly recognized, the decision to test itself can become a “litmustest by which relatives perceive and judge each other’s loyalty to the family” (Sobel andCowan, 2000) and predictive testing often produces a “ripple effect” across the familysystem (Kessler, 1994). Our findings that tested respondents experienced more GD thanthose who chose not to participate in testing are consistent with previous reports ofrelationship and communication changes within the family system following testing(Sobel and Cowan, 2000) and respondents’ perception of these changes asdiscriminatory (Bombard et al., 2007a).Contrary to expectations, discrimination in the health care, employment orgovernment settings was only cited by 4-8% of respondents, largely in reference to119getting medical care, work, doctors, other health professionals or when getting custodyand access to children. Despite significant concern for GD in the employment context(Harper et al., 2004), very little GD seems to be occurring in this setting. Furthermore,the low levels of GD in the health-care domain support the assumption that health careprofessionals have a better understanding of genetic risk, family history and test results,and likely use such information appropriately.Interestingly, tested respondents attributed their experiences of GD to their FHmore often than to their genetic test result. These results lend further support to thesimilar levels of discrimination seen between the tested and untested study groups:regardless of testing status, most individuals believed that FH was the predominantreason for their discriminatory experiences. These findings suggest that disease-relatedstigma is an important underlying issue and that more education and awareness ofgenetic disease is needed in our society. Respondents who tested positive, however,attributed their discriminatory experiences more often to both their FH and GTR. While itmay have been more difficult for these participants to differentiate betweenthe causes ofdiscrimination, it seemed that these two aspects are inextricably linked: only afterinquiring about one’s FH do third parties inquire further about genetic testing. Theinteractive effects of one’s FH and GTR may not be easy to discern retrospectively forindividuals after they have completed genetic testing. A prospective, longitudinal studyincluding (future) test participants and non-participants should be conducted to addressdifferences in experiences of GD before and after genetic testing. Nonetheless, thefinding that both GTR and FH are perceived to play an important role in discriminatoryexperiences points to the fundamental nature of the FH in people’s social interactionsregardless of testing status. Clearly, there is a need to shift the current focus of GD as agenetic testing issue to one which equally highlights the significant impact FH plays inpeople’s lives.Family history of HD was also found to be the major predictor of GD experiences.The effects of knowing one’s FH for a long period of time, becoming aware of the FH ata younger age and knowing individuals with HD symptoms or who have died contributedsubstantially to the likelihood of experiencing GD. These results further support thesignificant influence that the FH plays in individuals’ discriminatory experiences.Learning of one’s FH early in life likely impacts future insurance eligibility assessmentsand general life plans. Indeed, FH and experience with HD are important frameworksunderpinning individuals’ marital, reproductive, career and predictive testing decisions120(Cox and McKellin, 1999; Taylor, 2004). Moreover, age at perceived parental onset andknowledge of FH are significant factors in psychological functioning beforeand afterpredictive testing for HD (Decruyenaere et al., 1999; McAllister, 2002).These results point to the delicate balance involved in choosing the appropriatetime to inform children of their FH of HD and personal genetic risk. While studiessuggest that adult children prefer early disclosure of genetic risk and that growing upknowing about HD at an early age allows youth to cope better when relatives aresymptomatic (Forrest, 2007; Forrest et al., 2007; Holt, 2006), our results suggest thatdiscovering the FH at a young age increases their risk for GD. The question thusremains as to whether it is better to live a life as long as possible without the knowledgeof a potential impending disease or whether it is better to learn about one’s genetic riskearly and plan one’s life and manage the possible psychosocial consequencesaccordingly. Further research around these critical issues is warranted.It is important to note that psychological distress was found to be a significantoutcome of GD. The psychological consequences of GD to date have not been exploredand our results indicating associations between distress and GD are consistent withdocumented associations of distress with racial, gender, sexual and ethnic discrimination(Amaro et al., 1987; Landrine et al., 1995; Meyer, 1995; Williams, 1997). Moreover,psychological distress was not found to differ on the basis of perceived cause or group,this suggests that psychological distress is a fairly universal outcome of GD. Theseresults point to the need to view GD as a mental health and social issue that requiresappropriate counselling and support.The prevalence of insurance GD among persons at risk for HD was generallyconsistent with previous surveys of GD among other genetic and non-geneticpopulations, which indicate that 25-33% of individuals were denied life insurance oroffered it at a prohibitive rate (Kass et al., 2007; Lapham et al., 1996; Low et al., 1998).However, there are a few exceptions of note. An Australian study investigating the use ofGTR in life insurance underwriting decisions found only one case of a HD+ applicantdisclosing his GTR who received coverage at standard rates but the policy was limited to50 years of age (Otlowski et al., 2007). Moreover, persons with an HD+ GTR in the UK.are not declined life insurance even though insurers are permitted to use the HD GTRfor underwriting purposes of policies in excess of £500,000 (Otlowski et al., 2007;Secretary of State for Health, 2003). Furthermore, applicants with a FH of HD are notimposed higher premiums or ‘loadings’ (Otlowski et al., 2007). Thus, in practice, reported121experiences of GD in Canada may be more frequent than the U.K. because regulationsrestricting the use of genetic information by insurers are not in place and those with FHof HD are commonly required to pay higher premiums. Our results highlight the need forlegislative protection against GD in insurance as well as a need to pay special attentionto family and social domains during pre- and post test counselling.These findings are particularly important in light of the US federal geneticnondiscrimination bill (GINA) under consideration by the Senate. Given the availability ofa universal health care in Canada, similar legislation would allay GD in employment andextended health insurance plans. Such protections may ameliorate the increasedpremium rates for health insurance plans for those with a FH of HD. Although GD inemployment was not a frequent occurrence in this Canadian HD sample, GINA mayalleviate persons’ concerns for GD in this setting. However, GINA does not address thecommonly occurring life and disability insurance discrimination, the disrupted social andfamily relationships nor unfair treatment in health care and government domains.Other avenues are thus needed to assist persons at risk for HD and other geneticdisorders to mitigate GD. Discrimination affects all aspects of people’s lives; it impactsself-esteem (Link and Phelan, 2001) and, as the findings of the present researchindicate, limits their participation in our society. Clearly, comprehensive education andsupport programs are needed to inform and engage society about genetics to reduceignorance and the resultant level of stigma and discrimination. Support groups arecommon for many hereditary disorders and may be used to strengthen social supportnetworks and provide information and support for persons to lodge formal complaints inrelevant jurisdictions. Ultimately, structural interventions are necessary to change thesocial climate around genetic diseases. Given the vacuum of legal protection from GD inmany countries, current human rights legislation ought to include genetic information orfuture disability under the rubric of anti-discrimination laws.The current findings should, however, be interpreted in light of the study’smethodological limitations. Our findings are based on data from ten Canadian provincesand may not be generalizable to other jurisdictions. The cross-sectional design did notallow us to make definitive conclusions about causal effects of genetic status or FH onexperiences of GD. Longitudinal studies of the experiences of GD are needed. Inaddition, GD experiences were self-reported and could not be validated. Althoughdiscriminatory experiences are inherently subjective experiences, self-reports ofdiscrimination are commonly used. Previous studies have shown consistent122associations between self-reports of discrimination and health consequences rangingfrom mental health, substance abuse to physiological outcomes (Amaro et al., 1987;Landrine et al., 1995; Meyer, 1995; Williams, 1997).Our sampling strategy relied on reports of discrimination among personsattending clinics and participating in research. Individuals who actively participate inresearch and predictive testing may be more resourceful and better able to cope with thepsychosocial consequences of testing and/or research. The motivation and emotionalwell-being of people who are connected with clinics and participate in research orpredictive testing may therefore be unrepresentative of the general at risk HDpopulation. It is thus possible that our results represent an overly optimistic view of thenature and extent of genetic discrimination. Alternatively, study participants may be morecognizant of the issue of GD and thus be better able to recognize its occurrence. Finally,our measure of psychological distress was not a diagnostic instrument and can only beinterpreted as a sign of negative effect or emotional difficulty not as psychologicaldistress per se.This is the first study to report the nature and prevalence of GD amongasymptomatic individuals who have participated in genetic testing in comparison toindividuals who chose not to be tested. This is also the first study to distinguish betweendiscrimination based on FH and GTR, explore the breadth of GD across a wide variety ofsettings and examine the psychological impact of GD. Our findings demonstrate that GDis common in this sample, and that FH appears to be a major reason for and predictor ofexperiences of GD. Those who discover their FH at a younger age and know of their FHfor longer are also at greater risk for GD. Testing positive for HD is associated withincreased experiences of GD. Moreover, GD is a significant social issue and source ofdistress for persons at-risk for HD.123Total HD+ HD- Not Tested(n233) p-valuen % n % n % n %GenderFemale 153 65.7% 53 63.9% 52 61.9% 48 72.7%035°Male 80 34.3% 30 36.1% 32 38.1% 18 27.3%Average Age 45.5(117)b47.0 (110)b46.0(137)b42.9(9,5)b 009dMarital Status (n= 231)Married/common law 176 76.2% 64 79.0% 59 70.2% 53 80.3%0 27°Single/separated/divorced/widowed 55 23.8% 17 21.0% 25 29.8% 13 19.7%Education (n=226)Some college & above 206 91.2% 77 95.1% 72 88.9% 57 89.1%0 30°High school & below 20 8.8% 4 4.9% 9 11.1% 7 10.8%Employment (n=228)Employed 165 72.4% 56 68.3% 55 67.1% 54 84.4%Unemployed and seeking work 11 4.8% 4 4.9% 3 3.7% 4 6.3%Unemployed and not seeking work 52 22.8% 22 26.8% 24 29.3% 6 9.4%Children (n=232)One or more children 169 72.8% 61 74.4% 64 76.2% 44 66.7%040°Have no children 63 27.2% 21 25.6% 20 23.8% 22 33.3%CommunityISetting’ (n=233)Urban 192 82.8% 65 78.3% 73 86.9% 54 81.8%Rural 41 17.7% 18 21.7% 11 13.1% 12 18.2%0.34Time since testing (n=150)4 years or less 77 51.3% 37 50.0% 40 52.6% n/a5-9 years 35 23.3% 19 25.7% 16 21.1% n/a 0.80°10 years or greater 38 25.3% 18 24.3% 20 26.3% n/aTime since learning of FH (n=21 1)9 years or less 61 28.9% 23 29.9% 18 24.3% 20 33.3%10-19 years 56 26.5% 25 32.5% 15 20.3% 16 26.7%20-29 years 48 22.7% 15 19.5% 19 25.7% 14 23.3% 0.38°30-31 years 33 15.6% 11 14.3% 14 18.9% 8 13.3%4oyearsorgreater 13 6.2% 3 3.9% 8 10.8% 2 3.3%a Missing values are excluded, values are two-sidedb Values are mean (SD)C 2x3 Pearson chi-squared One-way anovae Does not meet assumptions of chi-square testBased on Statistics Canada’s rural postal code definition whereby indMduals with a 0 as the second character in their postalcode live in areas where there are no letter carriers and are considered to live in rural or small towns (ref: Statistics Canada. Ruraland small town Canada anlaysis bulletin, 3(3). November 2001).FH: Family HistoryTable 5.1 Demographic characteristics of respondents124TOTALSettinglltem n %Overall 93 39.9%Insuranceby life insurance company or agent 6327.00/nby long term disability company or agent 49 21.0%by mortgage company or agent 13 5.6%Familywhen making choices about having children 27 11.6%by family member . .. . 15 6.4%by spouse 13 5.6%Social..?ij44j:3“fir.tJ3JfrrIby friend 18 7.7%when estabiishing a relationshipØ$14 6.0%by boy/girlfriend 9 3.9%•.‘by’communr. 7 3.0%at school 5 2.1%by religious organization 2 0.9%Employmentatwork :..15 6A%when getting a job 7 3.0%Health Care . . . .. .twhen getting medical care 11 4.7%by doctor . 8 3.4%by other health care professional(s) 7 3.0%by genetic unseliflg service 5 2.1%Governmentwhen gettiAg access to or custody of children 5 2.1%in the law courts 4 l.7%by adoption agency 3 1.3%by blood bank 2 0.9%by Canadian Forceshtkto ZMa2 0 9%Respondents selected all that applied.Table 5.2 Experiences of genetic discrimination(Respondents reporting ‘yes’, they did experience discrimination as a result of either or both theirfamily history and genetic test result)125Tested(n167)NotTested(n=66)n%n%PVaIuea7142.5%2233.3%0.236HD+(n=83)HD-(n=84)NT(n66)n%n%n%PValueb4250.6%2934.5%2233.3%0.046TOTALn%Acrossallsettings9339.9%W1522.7%0.2023137.3%2226.2%1527%0.112FamiIy°3615.5%3118.6%57,6%0.044°1922.9%1214.3%57.6%0.034°-E9’°1f*25L50%461%007817205%895%461%0018°R.C.)Employment*166.9%159.0%11.5%•od1214.5%33.6%11.5%0.003°3’4h&thC8re*O88%1484%691%080211133%336%691%0081.Government93.9%95.4%00.0%d56.0%44.8%00.0%<*Categoriesarenotmutuallyexclusive-Da’oFishersexacttest.Valuesaretwo-sidedbPearsonchi-squaredtest.Valuesaretwosided‘D‘<coCD°Didnotreachsignficanceafteradjustingformultiplecomparisons0dDoesnotmeetassumptionsoftest0.CDcoYmCD g<C-0. -CD-CDX—.ø-D3C)0CD 0. Cl) C, -I 3 0) 0 D 0) Cl) 0) Co C 0hCD - CD 1 0 -‘1%) 0)ExperienceofGeneticDiscrimination(n181)Model1-UnadjustedModel2-AdjustedforAgeaModel3-AdjustedforSDFbOR(95%Cl)p-valueOR(95%Cl)p-valueOR(95%Cl)p-valueAge(years)0.96(0.93-0.98)0.001--0.95(0.92-0.98)0.004Female0.87(0.46-1.64)0.6690.77(0.40-1.48)0.4310.88(0.44-1.78)0.728CollegeorUniversityDegree2.03(1.04-3.97)0.0381.75(0.88-3.48)0.1131.74(0.84-3.57)0.134cuIncome$40,0001.39(0.77-2.51)0.2811.33(0.72-2.45)0.3631.23(0.60-2.51)0.568Haveatleastonechild0.95(0.48-1.87)0.8821.32(0.64-2.73)0.4481.35(0.59-3.07)0.477Marriedorcommonlaw1.27(0.63-2.58)0.5071.51(0.72-3.17)0.2771.32(0.58-3.01)0.509aEmployed1.68(0.83-3.39)0.1520.99(.44-2.21)0.9720.89(0.37-2.12)0.804Havelifeinsurance1.11(0.53-2.31)0.7831.21(0.52-2.40)0.7700.96(0.42-2.21)0.917Hadgenetictesting1.33(0.68-2.62)0.4111.65(0.81-3.34)0.1661.60(0.76-3.34)0.214KnownpeoplewithHDorwhohavediedfromHD3.51(1.44-8.56)0.0063.28(1.32-8.14)0.0113.36(1.33-8.50)0.010LearnedaboutFamilyHistory15yrsago2.05(1.10-3.79)0.0232.50(1.30-4.82)0.0062.63(1.33-5.18)0.005AgewhenFHwasdiscoverede-0.001-0.024-0.016DiscoveredFHunder18yrsold4.28(1.89-9.68)<0.00013.10(1.25-7.68)0.0153.39(1.33-8.63)0.0100DiscoveredFHbetween19-34yrsold4.18(1.82-9.62)0.0013.23(1.32-7.89)0.0103.55(1.42-8.86)0.007Respondentswereconsideredtohaveanexperienceofgeneticdiscriminationiftheyrespondedyestoeitherorbothofthefollowingquestions:HaveyoueverexperiencedgeneticdiscriminationinanyofthefollowingsituationsbecauseofyourfamilyhistoiyofHD7“Haveyoueverexperiencedgeneticdiscriminationinanyofthefollowingsituationsbecauseofyourgenetictestresults7Legend: aOddsratioswereadjustedforagebOddsratioswereadjustedforthefollowingsocio-demographicfactors(SDF):age,gender,education,maritalstatus,children,employment&income.CThereferencecategoryis35yrsandolder.-5.5 ReferencesAlmqvist,E.W., Brinkman,R.R., Wiggins,S., and Hayden,M.R. 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Race and health: basic questions, emerging directions. Ann. Epidemiol. 7,322-333.130Chapter 6: Discussion1316.1 INTRODUCTIONThe findings of this study provide a contribution to the ethical, legal and socialimplications (ELSI) produced by genetic testing and genetic discrimination (GD) inparticular. Since the beginning of the Human Genome Project and HapMap Project theinvestigation of ELSI issues has been recognized as an integral process of thedevelopment, testing and implementation of genomic advances (Collins et al., 2003;Foster, 2004).In this respect, the predictive testing program for HD serves as a model forgenetic testing programs. From its very inception considerable efforts have beendirected at understanding its benefits and psychological impacts. However, the risksofpredictive testing, particularly GD, have not been adequately addressed. Although GDwas a longstanding concern even before the introduction of the predictive testingprogram (Craufurd and Harris, 1986; Perry, 1981), little has been achieved inunderstanding or addressing this issue other than incorporating a discussion of thepossibility of GD in pre-counselling sessions (Broholm etal., 1994; Went, 1990).Unfortunately, HD is only a microcosm of the global realities of GD since theissue extends to other genetic disease groups as well as to the general population, bothof which have expressed significant fear of participating in genetic testing (Apse et al.,2004; Armstrong et al., 2003; Genetics and Public Policy Center, 2007; Government ofCanada, 2003) and genetic research (Hadley et al., 2003). The participation of large,diverse populations is required to ensure that genetic research studies are as valid andgeneralizable as possible. Many medical and social scientists alike have called ongovernments to respond to the public’s significant apprehension towards geneticsresearch, suggesting that the public’s reluctance to enter the genomics era will preventthem from “fully reaping the rewards of the investment already made in human genomeresearch” (Collins and Watson, 2003).These calls for action have begun to be heard and are currently being addressedthrough the implementation of various policy strategies, ranging from moratoria tolegislation proposals. The United States, for example, has proposed a federal billdedicated to the prohibition of the use of genetic information in health insurance andemployment decisions. While the bill, the Genetic Information Non-Discrimination Act132(GINA), has received wide support among scientists, disease advocates, health careprofessionals, and lawmakers, it remains stalled in the Senate, presumably because,among those definitional issues, opponents of the bills maintain that evidence of GD isscant. A comprehensive review of the literature supports their claim. Evidence of GDremains significantly hampered by anecdotal reports and methodological challenges.If the pace of scientific discovery is to continue and if society is to benefit fromthe potential diagnostic and treatment advances from genomics and genetics research,then the realities of GD must be investigated so as to advance these crucial policies.The findings of this study address these gaps and provide substantial evidence of GD. Aqualitative study offered an understanding of the issue from the perspective of personsat-risk for HD, the target of GD (Chapter 3), and contributed to the description ofstrategies used to manage the risk and experience of GD (Chapter 4). The developmentand administration of a national survey resulted in the description of the nature andextent of experiences of GD among persons at-risk for HD (Chapter 5). Perhaps equallyimportant is the elucidation of predictors of GD experiences as well as the possibleoutcomes of its effects on its target (Chapter 5). Integrating these findings into practiceand policy changes will likely contribute towards the ultimate goal of mitigating unfairdiscrimination on the basis of our most fundamental feature: our genes. Everyone shouldhave the right to benefit from the scientific advances of genomic medicine withoutdiscrimination.6.2 SUMMARY OF FINDINGSThe objective of this dissertation was to conduct qualitative and quantitativestudies to investigate the nature and extent of GD in a population at risk for HD.The first specific objective was to describe the concerns, experiences andstrategies regarding GD from the perspective of the HD community. To do this, semi-structured interviews were conducted with 45 genetically-tested and 10 untestedindividuals and analyzed using grounded theory methods. The findings demonstrate thata majority of individuals were concerned about (37/55) and reported that they hadexperienced GD (32/55) across a variety of contexts which extend beyond thetraditionally examined contexts of insurance and employment to include family, social,government and health care domains. A process of engagement with GD is described inwhich individuals formed meaningful interpretations of GD and personalized its risk andconsequences in their lives. Furthermore, depending on individuals’ level of133engagement with GD and the nature of the experience (actual experience of GD orconcern for its potential), four main strategies: “keeping low”, minimizing, preemptingand confronting GD were identified as mechanisms to manage GD.The second, third and fourth specific objectives related to identifying the natureand prevalence of experiences of GD and comparing these levels between persons whohave been tested and untested as well as by mutation status. The self-report, crosssectional survey results indicate that 93 respondents (40%) reported at least oneexperience of GD. GD occurred most often in reference to life insurance (n=63),disability insurance (n=49), making reproductive decisions (n=27), friends (n=18) andestablishing relationships (n14). Surprisingly, there were few reports of GD inemployment, health care and government settings (4-7%). GD did not differ in overallprevalence between the tested and not-tested respondents (n=71 vs. 22, P0.236).However, by mutation status, the proportion of respondents who experienced GD was atleast 16% higher in HD+ group than in the HD-(X2P=0.042) and NT(2P=0.045) groups(HD+: n=42 (50.6%), HD-: n=29 (34.5%), NT: n=22 (33.3%)). This suggests thatrespondents who test positive for HD are the most likely to report experiences of GD.Interestingly, there were also no significant differences in the proportions of GDexperiences between HD- and NT respondents (n=29 vs. 22,x2P 1 .00), suggestingthat testing negative for HD may not necessarily decrease the likelihood of experiencingGD.The fifth and sixth specific objectives were to identify the socio-demographicpredictors and health outcomes of GD experiences. The results demonstrate that familyhistory (FH), rather than genetic test result (GTR), was the major reason given forreported experiences of GD (GD based on FH: n=41 vs GTR: n=13 vs both: n=17). Inaddition to being an important reason for GD, the FH was also an important predictor ofGD experiences. The present study showed that those who become aware of their FH ata younger age (OR: 3.4-3.6, P=0.016), have first-hand experience with HD (OR: 3.4,P=0.01) and know of their FH for a longer time (OR: 2.6, P=0.005) are at greater risk forGD. Finally, psychological distress was a health outcome associated with the experienceof GD(X2:relationship between distress and GD based on FH: P0.0001 and GD basedon GTR: P=0.01 1). In fact, experiencing GD in more situations based on FH and GTRwas associated with increased levels of distress (Pearson R = 0.384 and 0.526,P0.0001, respectively). Moreover, levels of distress did not differ significantly between134perceived causes of GD (FH vs GTR vs both, Mann-Whitney U P>0.05) and geneticstatus (Mann-Whitney U P=O.721), suggesting that psychological distress is commonlyassociated with experiences of GD.6.3 INTEGRATING THE FINDINGSTo appreciate the contribution of the findings of this dissertation they must beplaced in context of the current literature in the field. This discussion will begin byreflecting on the conceptualization of GD, paying particular attention to its dimensionsand inherent subjectivity. Next, the findings related to the nature and extent of GD areconsidered in reference to each of the settings examined. Insight is also provided on theprofound effects growing up in a family affected by HD has on the individual as well associal dynamics to understand the importance of the FH in shaping GD experiences.Finally, the health outcome of GD is discussed in reference to other findings linkingdiscrimination and health.6.3.1 GENETIC DISCRIMINATION: A MULTIDIMENSIONAL CONCEPTThe qualitative findings of this dissertation contribute novel insight into theconceptualization of GD by those at-risk for or who have experienced GD. Engagementwith GD is a process which describes how individuals participants attempted to interpretthe meaning of GD and personalized its consequences into the context of their lives.Both these processes — interpretation and personalization - provide importantunderstanding of the multidimensional nature of GD, its dimensions and inherentsubjectivity.GENETIC DISTINCTIONS OR GENETIC DISCRIMINATION?Discrimination is defined as the process of making a distinction between thingswith the mind, or in action (The Oxford English Dictionary, 2007). The definition anddimensions of genetic discrimination, to date, have depended upon academicconceptualizations (Anderlik and Rothstein, 2001; Otlowski, 2005) and quantitativeinstruments (Apse et al., 2004; Kass et al., 2007; Lapham et al., 1996; Low et al., 1998),but what has been excluded is the perspectives of those at-risk or who haveexperienced GD themselves — the targets of stigma or discrimination.Genetic discrimination was conceptualized by those at-risk for or who haveexperienced GD as being unfairly prevented from doing something or being treateddifferently. Inherent in participants’ conceptualizations of GD were elements of legal and135social ideals. Human rights and privacy underpinned the unjust aspectsof GD forparticipants since it was similar to other forms of discrimination. Genetic discrimination,according to these persons, manifests from stigma and prejudice, elementshighlyintertwined and fundamental to GD. These conceptualizations resonate with broaderdefinitions of GD that pay due attention to the crucial elements of stigma, prejudiceandhuman rights.The terms used to elicit perceptions of GD influence the nature of responses.The qualitative investigation used the neutral term ‘differential treatment’, whichproduced both positive and negative outcomes following disclosures of FH or GTR.Individuals’ descriptions included advantageousas well as disadvantageousinteractions. Moreover, an important element for most participants interviewed wastheneed to include positive forms of genetic distinctions with the study of negativedistinctions. The term ‘differential treatment’, however, is not inherently neutralbecausesome abnormal treatment must occur (or be perceived) in order to distinguishit fromnormal, day-to-day interactions. Thus, genetic distinction is an all-encompassingconceptto describe the differential treatment, either negative or positive, relatedto geneticstatus. Moreover, it may be necessary to understand the positive forms of geneticdistinctions in order to appreciate why the converse was perceived as disadvantageous.Future work would thus be missing a vital component of the complete pictureunless allforms of genetic distinctions were included.SUBJECTIVITY: AN INHERENT COMPONENTThe nature of making distinctions is dependent on the perceptions belongingtothe target. What is considered ‘unfair’, ‘unacceptable’, ‘irrational’ or ‘different’isultimately a matter of debate, and depends on the target’s world view, culturalcontext,as well as what society deems appropriate or acceptable. Moreover, GD being groundedin social interactions requires individuals to make sense of others’ reactions andtheirown responses to them. The target’s perceptions may not necessarily includeor beconsistent with the intentions of the perpetrator. This process is thus inherentlysubjective in nature and is dependent upon many factors.There may be some individuals who accept and internalize the negative views ordiscrimination as “deserved” and hence view it as non discriminatory (Krieger, 1999). Asalluded to above, there may be differing views of what constitutes positive and negativetreatment. For example, monitoring the HD+ person for symptoms may be perceivedby136some individuals as caring behaviour while for others it may be considered unwantedand inappropriate. Self-representation biases, in which people may be (un)consciouslyshaping their responses to be “socially acceptable”, may be at play and participants mayalso vary their responses according to whether they find it helpful or distressing todiscuss such issues (Ross, 1989). Finally, people may exaggerate discrimination inorder to attribute blame to others instead of themselves (Neighbors etal., 1996).The effects of such biases in the interpretation of discriminatory insults mayimpact prevalence estimates as well as their effect on health (Krieger, 1999). Theexistence of such limitations, however, does not render studies on discrimination basedon self-report infalsifiable. Similar to the inherent subjectivity of reports of otherperceived health outcomes, these studies provide suggestive links between health anddiscrimination.Given the subjectivity inherent to discrimination, previous calls to ‘verify’ accountsof GD with the relevant third parties or via independent review (Treloaret al., 2004)seem inappropriate if not impossible. Instead, validation should focus on qualitativeapproaches to understand these perceptions to ensure they are reflected in quantitativetools intended to measure their prevalence and impact on health. Ultimately, thesubjective perception of the target is, and ought to be, sufficient to claim geneticdistinctions as discriminatory or otherwise.6.3.2 EXPERIENCES OF GENETIC DISCRIMINATION: THE NATURE AND EXTENTINSURANCE DISCRIMINATIONInsurance discrimination was the most common form of GD among individuals at-risk for HD. Nearly one in three respondents experienced insurance discrimination,largely by life and disability insurance companies, in the forms of insurance rejection,premium increases and requests to take a predictive test. Moreover, levels of insurancediscrimination were similar among all the respondents and were attributed mostly tohaving a family history of HD. These findings suggest that it is being part of an HDfamily, regardless of genetic status, that predisposes individuals to rejection, premiumincreases and requests to take a predictive test.These findings are generally consistent with previous surveys of GD among othergenetic and non-genetic populations, which indicate that 25-33% of individuals were137denied life insurance or offered it at a prohibitive rate (Kass et al., 2007; Lapham et al.,1996; Lowetal., 1998).These results do differ substantially from two studies concerning HNPCC andFragile X families. Among relatives of HNPCC patients, the prevalence of GD was foundto be 7% (Apse et al., 2004). Upon further investigation, these experiences were notrelated to their cancer risk but to other genetic and non-genetic conditions. AlthoughApse’s (2004) sample consisted of significantly more females, gender differences arenot known to affect experiences of GD. However, Apse’s definition of GD provided torespondents was: “when people or organizations make unfair decisions about someonewho is currently healthy based on genetic information”. The definition of GD provided inthe present study was: “being unfairly prevented from doing something, or being treatedunfairly” which was the interpretation of GD provided by the interviewees (Chapter 3 —forming meaningful interpretations). While Apse’s definition of GD is fairly comparable tothe one in the present survey since both definitions used ‘unfair’ to define discrimination,their definition involves decision making while ours necessitates treatment. Thisdifference would likely elicit different interpretations of GD and thus different responses.Moreover, the response format for the experience of GD question used by Apseet al. (2004) was left open-ended, while the present study required respondents toreview a list of 22 possible GD situations and check all that applied. The difference inresponse formats was also likely to contribute to prevalence differences, as respondentsof the present study were prompted to consider a wide range of scenarios, while Apse’sformat relied on the spontaneous recall of their respondents.A survey of insurance discrimination among 39 families diagnosed with Fragile XSyndrome reported no insurance cancellations, nor were carriers given increasedpremiums for any coverage purchased (Wingrove et al., 1996). Three families (7.7%) didreport that contract riders had been placed on their policies to exclude all Fragile Xrelated expenses. It is important to note, however, that in that study discrimination wasstrictly defined as the misuse of GI in insurance writing, which included cancellation ofinsurance for a child with Fragile X after genetic testing or refusal to insure carriers. Thisactuarial definition contrasts significantly with the broader definition used in this study,which likely accounts for the difference in prevalence of GD between the study ofWingrove et al (1996) and the study reported here.The issue of definition is an important one, as most studies of GD to date havedefined the term differently; this is an issue that would have substantial effects on the138prevalence of GD, notwithstanding the inclusion of symptomatic respondents or third-hand reports. Thus it is necessary to view these comparisons as informative but notconclusive.The comparison of the insurance landscape in Australia and the United Kingdompaints a different picture than experiences of GD in Canada. An Australian studyinvestigating the use of GTR in life insurance underwriting decisions found only one caseof a HD+ applicant disclosing his GTR. This person received coverage at standard ratesbut the policy was limited to 50 years of age (Otlowski et al., 2007). In comparison, in thecurrent study, there were 20 cases where HD- results were disclosed, suggesting thatmost individuals apply for life insurance prior to testing and those with HD+ GTR areself-selecting and deciding not to apply for life insurance all-together (Otlowski et al.,2007). In contrast, persons with an HD÷ GTR in the U.K. are not declined life insuranceeven though insurers are permitted to use the HD GTR for underwriting purposes ofpolicies in excess of £500,000 (Secretary of State for Health, 2003). Furthermore,applicants with a FH of HD are not given higher premiums or ‘loadings’ (Otlowski et al.,2007). Thus, reported experiences of GD in Canada may be more frequent than the U.K.because regulations restricting the use of genetic information are not in place and thosewith a FH of HD are commonly required to pay higher premiums.DISCRIMINATION IN THE FAMILYDiscrimination in the family must be viewed through a wider lens that capturesthe profound impact the presence of HD has on the family system. The following quotefrom Alice Wexler, a member of a prominent HD family, illustrates the initial discoveryand pervasive impact of HD on the family:First there is the grandfather who has died of “nervous trouble” on the back wardof a state hospital, the uncle who attracts whispers and stares from theneighbours as he staggers down the street, the doctor who says, “Women do notget it.” ... Divorce, arrests, abandonment, suicide punctuate the action. There isalways a moment of discovery, when the protagonists finally learn the truth,usually after having several children. In the end, the characters all come toresemble one another, and the actions winds down to a predictably gruesomeclose, with no resolution or release and always the promise of moreperformances to come ((Wexler, 1995) page xi).Often when HD is known to be present in a family it becomes part of that family’sidentity — part of its beliefs, norms, and values. Family myths surrounding the139transmission and expression of HD can be particular to a family. Pre-selection may evenoccur where one relative or child is singled out as likely to be carrying the HD mutationsince ‘he looks and acts just like dad’ (Kessler, 1988). Resource allocation, often in theform of attention and educational decisions, may also be influenced by the possibility offuture disease; thus, opportunities for those believed to be carrying the HD mutation maybe limited as resources are considered to be better directed elsewhere. Alteredexpectation and role assignment for the pre-selected person are typical outcomes suchas situations in which pre-selected individuals are given the task of caring for theiraffected parents since these individuals are expected to fail in school or their careers.While pre-selection is an unconscious process intended to control the uncertainty andanxiety inherent to HD, the process has profound psychosocial effects on the personassigned the “sick” role. While these occurrences are subtle in nature, they involvedefinite forms of differential treatment.It thus follows that the existence of genetic testing exerts added pressures on thefamily as a whole. It does not come as a surprise that the second most frequent settingfor GD is the family. It is also consistent that tested respondents reported moreexperiences of GD than those who chose not to participate in testing (n=31 vs. 5,P=0.044). Moreover, those who tested positive reported the highest levels of GD in thefamily (HD+ n=19 (22.9%), HD- n=12 (14.3%), NT n=5 (5.9%) P0.034). As others haveaptly recognized, the decision to test itself can become a “litmus test by which relativesperceive and judge each other’s loyalty to the family” (Sobel and Cowan, 2000) andpredictive testing often produces a “ripple effect” across the family system (Kessler,1994).Genetic testing has been shown to have a significant impact on familyfunctioning. Specifically, membership changes have been noted to occur as a result oftesting, positive or negative, causing rifts as well as re-connections among relatives. Forexample following negative test results family members have experienced distancingsince they have become free of the impeding disease and thereby lost previouscommunality of being “at-risk” with the family (Sobel and Cowan, 2000). Consistent withthe present findings, HD+ and HD- respondents reported GD among family memberswhereas those who did not test did not (HD+ n8 (9.6%), HD- n7 (8.3%), NT n0X2P=0.04). Alternatively, testing negative has given others the entitlement to disconnectfrom their family of origin for reasons that may include a desire to have a family in which140HD is not the basis for membership (Sobel and Cowan, 2000). The proportionofmembership changes following testing was reported by over 80%of anunrepresentative, interview sample of 18 families (55 participants) (Sobel andCowan,2000).The second area of family functioning reported to be affected by genetic testingis communication. Similar to membership changes, communication changesvary.Predictive testing could act to intensify previous patterns of communication or alterthepatterns altogether. Sobel and Cowan (2000) describe communication patterns in whichHD was considered a family secret and knowledge of HD was just part of the many“whisperings”. The interview and survey results support these trends as theyindicatethat significant changes in communication patterns occur following testing, especiallyforthose who test positive. Overall, 16 (10%) respondents reported communication patternchanges. These were more pronounced in the HD+ group compared to thosewho testnegative (HD+ n=12 (15.6%), HD- n=4 (5.3%)x2P=0.062). In comparison,communication pattern changes have been described by 50% of families interviewed(Sobel and Cowan, 2000). Open styles of communication have also been describedinwhich searching for symptoms in the mutation carrier was considered onefamily’s“favourite indoor sport” (Sobel and Cowan, 2000). In the presentstudy, symptommonitoring has been reported by 26 (15.6%) of respondents following testing, and,asexpected was cited mostly by HD+ respondents: (HD+ n=20 (26.3%), HD- n=6(8.0%),x2P=0.004)Recent work examining the impact of genetic testing on couples’ relationshipsprovides an additional basis for understanding these results. For the majority of couplespredictive testing appeared to have no overall adverse effect ontheir relationship, whichis consistent with the present findings indicating GD by a spouse was the least frequentsource of GD in the family setting overall (respondents reported GD in referenceto:reproductive choices n=27 (11.6%), by family member n15 (6.4%) and byspouse n=13(5.6%)).However, for a small number of cases there is breakdown of the relationship thatoccurs more frequently among tested-partner couples than untested-partnercouples inthe short-term (Richards and Williams, 2004). This supports the findings in the presentstudy indicating that tested respondents, specifically HD+ persons, reported more GDbyspouses than the HD- and NT groups (HD+ n9 (10.8%), HD- n3 (3.6%), NT n1141(1.5%)X2P=0.029).It seems that these issues stem from the differences in the quality ofrelationships perceived by tested persons and their partners following testing. Partnersreport more adverse effects following testing compared to carriers (Tibben et al., 1993b;Tibben et al., 1993a). Carriers rated the quality of the relationship higher than did theirpartners, and they perceived more positive changes (Decruyenaere et al., 2004). Ourfindings are further supported by various studies indicating relationship breakdown hasbeen noted to occur more frequently in carrier than non-carrier relationships: 10% vs.3% (Codori and Brandt, 1994), 24% vs. 10% (Tibben et al., 1993a) and 20% vs. 10%(Sobel and Cowan, 2000).Contradictory findings have been reported where marital adjustment issues aremore pronounced among non-carrier couples than among relationships that involve acarrier (Richards and Williams, 2004). Factors found to be associated with theseperceptions were the (premature) changing roles that induced post-test marital distress,which may explain this discrepancy (Decruyenaere et al., 2004; Sobel and Cowan,2000).Cleary there are profound impacts of genetic testing on the family system. Thefrequency of family GD and its nature, exemplified by symptom-monitoring,communication changes, a perceived lack of closeness or support, and pressure fromrelatives regarding reproductive, educational and marriage decisions are consistent withpreviously described disturbed interactions in the family following testing. Moreover, theassociation between the likelihood of experiencing GD and the length of time and type ofexposure to the FH of HD is consistent with studies indicating altered behaviour andfunctioning in families with long-standing histories of HD (Kessler and Bloch, 1989;Sobel and Cowan, 2000). Evidence of pressure during reproductive decision making isalso consistent with previous work indicating that the opinions and choices of relativesregarding reproduction (Downing, 2005) are a source of competing interests andpriorities to contend with during reproductive decision-making.Taken together, the availability of predictive testing produces pressures andreactions towards those who test as well as those who choose not to test. While theseissues are reflected in the current findings, a broader exploration of GD in the context ofthe family unit as a whole may provide a better appreciation from a holistic, familysystems perspective.142DISCRIMINATION IN SOCIAL CIRCLESSocial circles were the third most frequent settings in which GD was reported.Overall 12.4% of respondents believed that they were discriminatedagainst, mostly byfriends and when establishing relationships. These findings were moreprevalent amongtested respondents than untested respondents. Specifically, the HD+ respondentsreported more than twice the level of discriminationas the other groups. This isconsistent with findings from work on the impact of genetictesting on couples’relationships (Codori and Brandt, 1994; Sobel and Cowan, 2000;Tibben et al., 1993a).Although these studies focus on established relationships and not establishingrelationships, they elucidate trends that may be expected when HD+persons developnew relationships. Extrapolating from the finding that tested couples, particularly carriercouples, experience adjustment difficulties, it is hypothesized thatthe same would occurwithin newly formed relationships, and the present findings areconsistent with thishypothesis.Overall, the findings that experiences of GD occur most often reported ininsurance, family and social settings are consistent with the study’s overall theoreticalassumption that GD is situated in the social interactions and consequencesthat occurfollowing disclosure of one’s risk or genetic status. Indeed insurance, familyand socialcontexts are the most likely contexts in which disclosure (or discussion)of one’s FH orGTR would take place, and thus it is not surprising that these were the settings in whichGD occurred most often.EMPLOYMENT DISCRIMINATIONContrary to expectations, GD in employment settings was reported by only 6.9%of respondents and was largely in reference to current working conditions as opposed toduring the hiring process. These findings are consistent with individuals’ qualitativedescriptions of limits to opportunities in the workplace, denials of promotions andforcedretirement, all of which involve current working conditions. The qualitativefindings alsohighlighted individuals’ tendency to avoid seeking new employment out of fear of GD,which may explain the surprisingly low levels of GD in this setting. Furthermore, it mayalso be possible that individuals consciously seek work where GD is unlikely.Thesehypotheses may explain the findings that experiences of employment GD significantlydiffered between tested and NT groups (n=15 vs. 1, P=0.045), where significantly moreHD+ respondents reported employment difficulties than both HD- and NT respondents143(HD+ n=12 (14.5%), HD- n=3 (3.6%), NT n=1 (1.5%)x2P=0.003 — did not reachsignificance after adjusting for multiple comparisons).Employment GD reported in the present study was considerably lower than inprevious reports. Among 332 members of genetic support groups, 13% reported beingdenied or let go from a job (Lapham et al., 1996). Another study of adults or parents ofchildren with cystic fibrosis, sickle cell disease, diabetes and AIDS found that 19% of allrespondents were not hired due to their medical conditions and those with geneticconditions experienced significantly more GD than those with non-genetic conditions(Kass et al., 2004). It is important to note that both these samples consisted ofsymptomatic respondents. Among the respondents who were at-risk for cancer in Kass’sample (2004), reports of employment GD were 0-4.17%. Thus, it is possible that thesedifferences in the prevalence of employment GD may be largely due to the presence ofsymptoms and do not entirely represent GD based on genetic information (GI) alone.GOVERNMENT & HEALTH CARE DISCRIMINATIONThere was little evidence for GD in health care and government settings. Themost compelling findings were discriminatory issues in reference to getting medical careand by doctors, which were cited most frequently (respondents reported GD in referenceto: getting medical care n=1 1 (4.7%), by doctor n=8 (3.4%), other health careprofessionals n=7 (3.0%) and by a genetic counseling serviceflt5(2.1%)). Asrespondents’ reports indicate, directive counselling regarding reproduction was aprominent issue. Related surveys on the attitudes of medical professionals revealdisconcerting insights. Elger and Harding (2003) found that Swiss medical students aredirective in some counselling situations and exhibit eugenic pressureson anddiscrimination against persons at-risk for HD (Elger and Harding, 2003). Specifically,they reported that 39.4% of medical students agreed that society should do everythingpossible to diminish the frequency of HD, including non-governmental pressure oncarriers to undergo systematic genetic testing and recommendation of sterilization (Elgerand Harding, 2003).Chinese geneticists’ eugenic views are even more striking: 86% of geneticistssurveyed believe that governments should require premarital carrier tests and thatcarriers of the same gene mutation should not mate with each other (91%). In the caseof HD, 85% supported the notion that children should be tested for the gene mutation144(Elger and Harding, 2003). It must be acknowledged, however, that theseviews aredeeply embedded in a culture that promulgates “improving the quality of the newborn”asmandated through their Maternal and Infant Health Care Law(1994). This law requirescouples planning marriage to undergo genetic screening for genetic and infectiousdiseases and mental disorders. Any couples carrying disease-related mutationsarepermitted to marry only if they agree to sterilization or long-term contraception(UnitedNations Economic and Social Commission for Asia and the Pacific, 2007).Societal attitudes towards individuals with a perceived future disability or diseasepredisposition reflect social and cultural values and foster beliefs that influence attitudesand behaviour. Thus, unsolicited pressure on reproductive choices anddirectivecounselling are but two elements of health care influences that devalue individuals’personal control and free informed decision making. Effortsto address GD need toextend to health-care and government settings.6.3.3 FAMILY HISTORY: THE FUNDAMENTAL ISSUEFamily history (FH) was found to be the major cause and predictor of reportedGD experiences. A large majority of respondents attributed their GD experiencestotheir FH (GD based on FH: n=41 vs GTR: n=13 vs both: n=17). In fact, allaspectsrelated to the FH of HD, including length of time one is aware of their FH (OR: 2.6,P=0.005), age when one becomes aware of HD (OR: 3.4-3.6, P=0.016), and thetype ofexposure to HD one has had (OR: 3.4, P=0.010), significantly impacted on the likelihoodof experiencing GD. These findings highlight and confirm the profound effects growingup in a family affected by HD have not only on individual and family dynamics but, asthepresent findings indicate, on social relationships and interactions.HD is a family disorder (Brouwer-Dudokdewit et al., 2002; Sobel and Cowan,2000; Vamos et al., 2007). Indeed growing up in a family with a long-standing historyofHD introduces specific stressors that may influence the relationship between parentsand children (Brouwer-Dudokdewit et al., 2002; Vamos et al., 2007). With the onsetofdisease come disturbing personality changes such as a depression and aggression,which may be frightening for children and strain the parent-child bond. Onsetof diseaseoften results in changes to the structure of the family, in which the unaffected parenttakes on greater responsibilities, shifting the general household structure and attentionto children even further (Vamos et al., 2007; Van der Meer et al., 2006). At times, these145changes and responsibilities may become too large burden to bear for unaffectedparents and may cause them to leave the household. Children may then take up the roleof caregiver, which can have far-reaching emotional, psychological and behaviouralimpact (Forrest et al., 2007).Even prior to the onset of disease, the existence of HD in the family has beenshown to have severe impact on family functioning in terms of low cohesion andexpressiveness and high levels of conflict (Vamos et al., 2007). In fact 80% of adultchildren in HD families reported that “it’s difficult being part of a family with HD”, andanother 40% admitted that “HD split us apart” (Vamos et al., 2007). In fact research andclinical experience suggest that young people growing up in families affected by HD mayexperience social and emotional difficulties and may experience adverse effects on otherdevelopmental phases of adolescence such as establishing peer relations,independence and the initiation of intimate relationships (Forrest et al., 2007).Some of these difficulties stem from a lack of secure attachment representationsbetween parent and child, in which the instinctual need to form close affectionate bondsis not met (Van der Meer et al., 2006). These alterations lead to lack of emotionalsecurity and have been associated in difficulty maintaining social relationships (Van derMeer et aI., 2006). Moreover, childhood experiences of HD and growing up in adisordered household are known to contribute to conduct disorder in adolescents andantisocial personality disorder in adults (Folstein et al., 1983). Regression analysesamong persons requesting predictive testing has shown that the younger persons wereat the parental onset of HD, the more likely it was that they would have lower egostrength, greater anxiety, and a higher level of depression in the period before testing(Decruyenaere et al., 1999). Beyond the intra-personal level, when HD is known tosegregate in a family, shame, stigma or social isolation of the family often may ensue.Growing up in a family affected by HD has far-reaching impacts and, as suggested bythe present study’s findings, has influence on individuals’ experiences and attributions ofGD. Not only does HD affect the life-cycle of a family as well as the social functioning ofits members but also their perceptions of how people treat and interact with them.In regards to insurance, having a FH and knowing of this risk for a longer timehave direct impact on insurance underwriting. Concealing this information is illegal, andthe earlier one is aware of a FH, the greater the impact the FH information has on allfuture eligibility and premium assessments. This situation is analogous to the hereditary146cancer context, in which risk for breast and colorectal cancer has been shown to lead topremium loadings on life insurance as well as denial of critical care and disabilityinsurance (Norum and Tranebjaerg, 2000; Otlowski et al., 2007).Ultimately, because of the psychiatric, cognitive and motor disturbances in HDpatients, family dynamics in families affected by HD differ significantly from those in nonHD families (Folstein, 1991; Kessler and Bloch, 1989). These dynamics form crucialframeworks for personal decision-making regarding reproductive, marital, career andpredictive testing choices (Cox and McKellin, 1999; Taylor, 2004). Furthermore, assuggested by the findings of the present study, these dynamics also influence socialinteractions and experiences of differential treatment: the greater the exposure one hasto HD in the family, the greater the influence exposure to HD has on perceptions andexperiences of GD.6.3.4 PSYCHOsocIAL IMPACT OF GENETIC DISCRIMINATION: DISTRESSFrom a century of epidemiological research, it is now established thatdiscrimination harms health (Krieger, 1999). Inequality of various kinds has been shownto be associated with health consequences ranging from mental health, substanceabuse to physiological outcomes. Examples include: sexual discrimination resulting inelevated rates of smoking, suicide and substance abuse (Council of Scientific Affairs,1996), disability discrimination associated with denial of health insurance thus resultingin inadequate medical care (Gill, 1996), age discrimination associated with poorersurvival of the elderly due to less aggressive treatment (Minkler and Estes, 1991), socialclass discrimination associated with excess morbidity and mortality (Williams andCollins, 1995), racial discrimination associated with higher mortality rates (NationalCenter for Health Statistics, 1997), and gender discrimination associated with sexualabuse and fewer years of disability-free life (adjusted for life expectancy) (Bachman andSaltzman, 1995; Cosentino and Collins, 1996; National Center for Health Statistics,1997). It stands to reason that GD would also result in adverse health consequences.Results from the present study suggest that this is indeed the case. High levelsof psychological distress were significantly associated with reported experiences of GD.Given the well-documented associations between other forms of discrimination andhealth, these findings are not surprising and support previous associations betweendistress and racial, gender, sexual and ethnic discrimination (Amaro et al., 1987; Brown147et al., 2001; Jackson et al., 1996; Landrine et al., 1995; McNeilIy et al., 1996; Meyer,1995; Williams, 1997; Williams et al., 2003). Still, the health impact of GD has not beendescribed before, raising the effects of GD to a level that suggests it ought to berecognized as a significant mental health concern in addition to an economic or policyissue. With the recent establishment of a Canadian Mental Health Commission, mentalhealth discrimination has become a policy priority in Canada. It is hoped that thesefindings may contribute to similar measures related to GD.6.4 PRACTIcE RECOMMENDATIONSINTRODUCTIONGD is one of the major ethical and professional challenges for geneticprofessionals, including genetic counselors, physicians and nurses (McCarthy Veach etaL, 2001). Genetic counsellors encounter reports of discrimination among clients at afrequency of 29% (Bower et al., 2002). Thus, the results of the present study may behelpful for genetic professionals supporting clients confronting issues of GD.Genetic counselors practicing in the U.S. routinely discuss GD in cancer genetics(Pfeffer et al., 2003). Their discussions typically include a definition of GD, descriptionand limitations of federal and state legislation, types of insurance (e.g., health, life anddisability), prevention strategies and examples of discrimination (Pfeffer et al., 2003).However, over 40% of genetic counselors indicate they do not discuss particular topicsconsistently with all their cancer clients (Pfeffer et al., 2003). In fact, anecdotal evidencefrom the qualitative component of the present study suggests that discussions on GDare not uniform or consistent across Canadian HD testing centres.Engaging clients in discussions of GD is essential. The National Society ofGenetic Counselors (NSGC) Code of Ethics states that genetic counselors should“enable their clients to make informed independent decisions.. .by providing orilluminating necessary facts” (National Society of Genetic Counselors, 1992). Thechallenge appears to lie in determining what constitutes an appropriate balance betweeninformed consent and perpetuating the perception that GD exists or is widespread.Indeed an inherent tension exists in the process of discussing GD.148Discussing GD in an abstract fashion where the risk of GD is not put into contextdoes indeed instill a perception that GD exists or is widespread (see ‘nature of theawareness events’ in Chapter 3). However, coupling the provision of information aboutGD with opportunities for clients to discuss concerns about and past experiences withGD is likely to be helpful in supporting the process of personalizing the factualinformation presented about GD and identifying strategies to minimize or manage theconsequences of GD. Thus, the framework of engagement with GD and survey findingsmay provide clinicians with helpful tools to direct such discussions and suggest ways tomitigate GD.PREDICTORS OF GENETIC DISCRIMINATIONGiven the present findings, it would be helpful for genetic professionals to stressthat having a FH of HD was the major reason given for individuals’ GD experiences.Moreover, participating in genetic testing itself was not significantly associated withexperiences of GD. While it is true that HD+ persons reported significantly higher levelsof GD than HD- and NT groups, the HD- and NT groups also reported GD, and at similarlevels as a consequence of having a FH of HD. In other words, while testing positiveadds an extra layer of burden to bear, those who do not undergo testing and those whodid and tested negative, both report similar levels of GD because of their FH.While the FH is the major cause given for GD, the nature of the FH was also animportant predictor of who was most likely to experience GD. Individuals who had firsthand experience with HD symptoms or death, discovered their FH at a younger age orknew about their FH for over 15 years were 2.6-3.5 times more likely to experience GD.Thus, it may be helpful for genetic professionals to pay particular attention to clients whohave first hand exposure to HD, learned about their FH earlier in life and have knownabout their FH for longer, since these clients are at greatest risk for GD.These findings are consistent with counselling experience indicating thatmembers of new mutation families have distinct counseling needs compared toindividuals who grew up in HD families (Maat-Kievit et al., 2001) A new mutation familyrefers to a situation in which a family member is clinically diagnosed with HD without aprior family history (Semaka et al., 2006). Relatives, namely siblings, of new mutationpatients become eligible for predictive testing given their new genetic risk for HD.Candidates for testing who are unexpectedly confronted with the risk for themselves,149their offspring, and relatives find this uncertainty difficultto deal with. In order to restorecontrol over their lives, new mutation testing candidates are generallyknown to seektesting as soon as possible, potentially at the expense of becoming awareof the fullramifications of testing (Maat-Kievit etal., 2001) and understandingHD. One may furtherspeculate that since new mutation candidates generally learn of their risklater in life,after insurance arrangements, career and reproductive decisionsare set in place, theyare less likely to be at-risk for GD. In fact this relationship is consistentwith the study’sfindings, which indicate that those who learned of their FH after theage of 35 aresignificantly less likely to experience GD. An alternative explanationis that individualsthat became aware of their FH earlier simply had more time to encounterGD. (It shouldalso be noted that in the Canadian context, new mutation familiesdo not seek testing asfrequently (Hayden, 2007)).MANAGEMENT OF GENETIC DISCRIMINATIONIn light of the current vacuum of legal protection from GD in Canada anda manyother countries, genetic professionals may be in a unique positionto help testingcandidates mitigate fears and experiences of discrimination.Non-directiveness has been a central tenet of genetic counseling since its formalinception and is a principle of the NSGC Code of Ethics (National Societyof GeneticCounselors, 1992). The NSGC Code of Ethics further states thatgenetic counselorsshould be “illuminating anticipated consequences.. .and prevent discrimination on thebasis of genetic status” (National Society of Genetic Counselors, 1992). Althoughgenetic counselors have traditionally ascribed to value-neutral non-directive counseling,some authors have called on genetic counselors to adopt a more directive approach intheir counseling (Bowles Biesecker, 2000; Kessler, 1992). This recommendation isechoed for the purposes of managing GD.Genetic professionals should continue to urge candidates to secure desiredlevels of insurance before proceeding with testing and make the possibleimplications ofthe test results on future insurance assessments explicit. In fact, some authorsrecommend that the informed consent process for cancer testing include an“individualized assessment of insurance and employment discrimination risks” (Stopfer,2000). The results of the present study support this recommendationand suggestextending these discussions into the familial and social contexts. A pre-test discussion of150the possible impact of the test result on relationships, including marital, sibling, parental,romantic and platonic, should result in a better preparation for and more understandingof the reactions after testing.A cursory discussion of GD limited to the informed consent process is notsufficient. Rather an independent, explicit part of pre-test counselling is preferred inwhich plans for disclosure of GTR or lack thereof should continue to be discussed,paying particular attention to employment, family and social contexts. During suchdiscussions clients’ past experiences and concern for GD can illuminate previousapproaches used to manage GD. Professionals should be aware that unengagedstigma-related coping strategies have been associated with adverse physicalconsequences such as hypertension (Krieger and Sidney, 1996).Further strategies to mitigate GD may include withholding information frominsurers and employers, as well as from candidates’ medical records. It is not unusualfor genetics clinics to maintain shadow charts (Bower et al., 2002). These can be usedfor the purposes of predictive testing for those candidates who are particularlyconcerned about possible GD for themselves or families and may otherwise denythemselves the possible benefits of testing such as possible psychological relief and/orplanning opportunities. Similarly, it may be recommended (as opposed to simply beingoffered as it currently is in some clinics (Benjamin et al., 1994)) that a letter not be sentto family physicians so that they, along with insurers and employers, would be unawareof the candidates’ involvement in the predictive testing program.A final strategy involves anonymous predictive testing. Several Americans at-riskfor HD have sought predictive testing in Canada under the auspices of anonymity, in fearof health insurance discrimination for themselves and their families (Burgess et al.,1997).Indeed these strategies raise salient issues. Clinicians cooperate in excludinginsurance companies and employers from risk information when a public policy responsewould be preferable. Candid discussion with candidates about the implications of thesestrategies is strongly recommended. This will ensure that candidates are aware of therisks: insurance contracts may be subject to annulment and, more importantly, optimalcare, such as appropriate counseling and follow up, may be compromised because ofthe discontinuity of information in an individual’s medical files and between health careprofessionals.151AVENUES FOR RECOURSEDiscussion of the relevant laws and avenue for recourse is likely to be helpful,not only to inform patients that differential treatment based on perceived future disabilityis discriminatory, but to empower patients with the means to address futurediscriminatory issues. Professionals may wish to discuss the availability and purposes ofprovincial human rights commissions as well as labour unions for employment disputes.Ongoing contact with genetic professionals would also be helpful, as this allows thegenetic professional to be the point person for any future GD issues, if any. Moreover,this would ensure that individuals may be referred for additional counselling or legalcounsel specializing in human rights issues where appropriate.6.5 POLICY RECOMMENDATIONSINTRODUCTIONGenetic testing is becoming a vital tool in the standard armoury of clinicalmedicine, which makes it increasingly difficult to distinguish genetic information fromhealth information. There are over 1000 genetic tests that utilize DNA-based,cytogenetic and biochemical methods to determine underlying causes of both geneticand non-genetic diseases in persons who may be symptomatic or asymptomatic. This isthe nature of clinical medicine, which is likely to become more complex as advances inpharmacogenomics and preventative medicine continue to push the boundaries ofhealth care.A less genetic-centric approach is clearly required, which considers theadaptation of current protections as well as the creation of novel ones. These mayinclude public and professional awareness and, ultimately, an anti-GD law.PUBLIC & PROFESSIONAL AWARENESSContrary to the U.S. where GD is a ‘somewhat of a household word’ (Barash,2000), the issue has received little attention in the Canadian media or general discourse.The lack of legislative debate, along with the presence of a universal health care system,creates the impression that GD may not be a relevant issue in Canada. However, thepresent study’s findings suggest the contrary: experiences of GD are common and GD is152a real concern for those at-risk for HD. Other studies suggest it is a significant problemamong other genetic populations (Apse et al., 2004; Armstrong et aL, 2003;HaIl et al.,2005). It would thus be helpful to initiate public discussion and educational campaignsabout genetics and genetic disease. Increasing public awareness about genetics,genetic research and ELSI may have the added benefits of reducing fears of GD andstigma related to genetic disease as well as encouraging engagement with geneticmedicine and participation in genetic research. Public awareness campaigns forgenetics have been successful in Australia and the U.K., where genetics educationcentres have been established to promote public engagement and professionaleducation on genetics and public health campaigns have been established to encouragegreater discussion with families and GPs about FH of genetic disease (Centre forGenetics Education, 2007; North West Genetics Knowledge Parks, 2007). Such centresare lacking in Canada and are needed to fill this apparent gap in public engagement andeducation in the areas of genetics, public health and social issues.In conjunction with these public awareness efforts, education of health careprofessionals, especially genetic professionals, should include an overview of GD andrelated legal protections. In this way discussions on the current climate of legalprotections against GD may become an integral component of pre-test counseling for alladult-onset hereditary conditions for which presymptomatic testing is available inCanada.On a fundamental level, it may be also be helpful to make insurance andemployment decisions more transparent, to ensure that GI is not being used to thedetriment of individuals or their families and communities. Public awareness of thesedecision-making processes may help dispel erroneous beliefs as well as reduce fears ofGD.ANTI-GENETIC DISCRIMINATION LEGISLATIONThe results of the present study provide knowledge for direct use by policy-makers. First, the present findings suggest that the concerns and experiences of GD arevery real and, most importantly, common among persons at-risk for HD. Previous claimsthat GD is a “rare” occurrence (National Society of Genetic Counselors and FORCE:Facing our risk of cancer empowered, 2004; Walker, 2007) are untrue. Second, theperception among those at-risk for GD is that treating people who do not have symptomsof disability unfairly is a human rights issue that should be forbidden by law similar to153discrimination against disabled people. Thus the policy imperative to address the fearsof GD and experiences is justly supported.Third, the findings clearly suggest that any definition of GI should include familyhistory, since it was perceived by most respondents as the major reason for experiencesof GD, despite testing status or results. Finally, any policy discussion will need to includeprotection from GD in life, disability and long term care/disability insurance policies,since these areas were found to be areas of significant concern for and experiences ofGD.6.6 FUTURE RESEARCH DIRECTIONSThe data presented in this dissertation suggest numerous avenues for futureinvestigation. This includes qualitative and quantitative approaches aimed atunderstanding the full extent of GD and respective health outcomes.MECHANISMS OF RESPONSE TO GENETIC DISCRIMINATIONWhile it is now established that psychological distress is associated with GD; it isunknown whether other psychological and possible physiological responses occur as aconsequence of GD. Moreover, it is unclear whether or how psychological, and possiblephysiological responses, are mediated by GD, if at all.This may be achieved by many means, but an individual-level approach usingcross-sectional and longitudinal data may be best. An individual-level approach wouldexamine whether self-reported experiences of GD are associated with specified healthoutcomes, using instruments aimed at measuring the relevant outcomes such asphysiologic responses (cardiovascular, endocrine, neurologic, immune, etc.) and/ormore general health outcomes (psychological distress, self-rated ill health, psychologicalwell-being, stress, depression, quality of life, etc.). Ultimately, however, longitudinalstudies are needed to fully appreciate the impact of GD on health on time and mayprovide further insight on the mechanisms of response to GD.CONCERN FOR GENETIC DISCRIMINATION: A MAJOR FACTOR?While findings from the present study provide a rich description of individuals’concerns for GD, it is unknown how these concerns influence behaviour andmanagement strategies among persons at-risk for HD. For example, do these concerns154influence at-risks persons’ participation in genetic testing or genetic research? Suchtrends indeed exist among other populations, and until they are examined they can notbe addressed to ensure that the concern for GD does not hinder the potentiallybeneficial engagement with genetic testing and research.Furthermore, given the integral role concern plays in responses to GD,investigating the extent and influence of concern for GD in the HD population will providea more holistic appreciation of GD. For example, does concern precede or mediateresultant distress? Do particular types of GD lead to greater amounts of concern (andthus distress)? Is concern for GD associated with physiological responses, and if sohow?THE MULTIPLE TARGETS OF GENETIC DISCRIMINATION: WHAT ABOUT THE FAMILY MEMBERS?HD and GD affect families. Given that a large motivator for undergoing predictivetesting among individuals at-risk for HD is to inform (and thus benefit) their children, it isseem likely that individuals have concerns about how their GTR, including GD, mayimpact their children. Findings from the present study suggest that individuals havesignificant concerns for GD for their children. Thus the extent of GD may be under-represented if experiences of and concern for GD for family members is not taken intoaccount. Clearly, understanding how and if GD impacts other family members isnecessary to achieve a complete appreciation of how GD, like HD, affects people’s andfamilies’ lives.NEW MUTATION FAMILIES: AN IDEAL COMPARISON GROUPGiven the fundamental influence the FH has on GD experiences, it would behelpful to compare GD experiences among individuals who are at-risk for HD but whohave not been aware of their FH for a significant period of time. This would ultimately bethe ‘litmus-test’ for the significant influence the FH has on GD experiences. Arguably,this hypothesis has been tested in the regression models that demonstrated thatrespondents who became aware of their FH when they were 35 years or older aresignificantly less likely to experience GD than to those who discovered their FH earlier.However, it is not certain that these respondents are in fact new mutation families orwhether the FH was not known to these particular respondents due variouscircumstances surrounding the family communication of HD.New mutation families, in which no FH existed prior to a relatively recentdiagnosis of a family member (Semaka et al., 2006), generally learn of their risk later in155life, after insurance arrangements, career and reproductive decisions are set in place,are less likely to be at-risk for GD. Thus, these individuals would be an ideal comparisongroup in which to test the hypothesis that those who do not have (as opposed to notaware of) a FH of HD do not encounter GD, or at least at lower levels than those that donot test. This approach may further establish the fact that it is knowingly being part of anHD family, regardless of genetic status, that predisposes individuals to GD.THE FULL EXTENT OF GENETIC DISCRIMINATION: CONSIDERING FREQUENCY, DURATION & TIMINGThe present study is the first to report on the nature and prevalence of GDamong persons at-risk for HD, explore the breadth of GD across a wide variety ofsettings and examine the predictors and outcomes of GD. However, what has not beenachieved is an understanding of how often particular types of GD occur, for how longand at which point in time. While insurance GD was reported most often, this form of GDmay have occurred relatively infrequently, given the fact that individuals typically applyfor insurance a small number of times, and at particular stages in their lives. On thecontrary, family and social GD may actually occur more frequently and for longerdurations. Given the fundamental impact of the FH on GD, it is conceivable that GD insocial and familial contexts is more pervasive and perhaps more distressing than GD inother contexts. Likewise, employment GD was cited by few individuals, but in terms ofday-to-day functioning or job-related tasks, the frequency at which this form of GDoccurs or pervades peoples’ fears and decisions is unknown. Survey instrumentsdesigned to address frequency, duration and timing of particular forms of GD arewarranted to appreciate the full extent of the issue as well as its definite impact on healthoutcomes better.6.7 CONCLUSION“We know that if one man’s rights are denied, the rights of all are endangered’(Robert F. Kennedy, 1966). The findings of this dissertation have implications beyondHuntington disease. Indeed as a classic monogenic disease fundamental principles ofthe HD predictive testing program have served as a model for presymptomatic testingprograms for genetic and non-genetic diseases (Hayden, 2003). Likewise, the findings ofthis dissertation provide additional insight for genetic screening programs for diseaseswith small effect genes as well as other late onset and neurological conditions. Even withits relatively high test validity and penetrance, this study highlights the importance of the156HD family history in persons’ experiences of GD. Irrespectiveof the predictive validity ofa genetic test or the penetrance of a genetic mutation fora disease, having a familyhistory of disease plays a fundamental role in the perceived experiences of GD.As the first study to investigate the nature and extent of GD among anasymptomatic tested and untested population, this dissertation provides evidencethatGD is a frequently reported experience and a source ofdistress for persons at-risk forHD. It is hoped that these findings will provide insight for policy, identify areaswheremore education and support is needed, and provide directionto genetic professionalssupporting their clients as they confront issues of GD.1576.8 REFERENCESAllison K.W. (1998). Stressed and oppressed category membership. In Prejudice: The targetsperspective, J.K.Swim and C.Stangor, eds. (San Diego, CA: Academic),pp.145-170.Almqvist,E.W., Bloch,M., Brinkman,R., Craufurd,D., and Hayden,M.R. (1999). 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