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Genome-wide and transcriptome-wide association studies of mammographic density phenotypes reveal novel loci Chen, Hongjie; Fan, Shaoqi; Stone, Jennifer; Thompson, Deborah J.; Douglas, Julie; Li, Shuai; Scott, Christopher; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Michailidou, Kyriaki; Li, Christopher; Peters, Ulrike; Hopper, John L.; Southey, Melissa C.; Nguyen-Dumont, Tu; Nguyen, Tuong L.; Fasching, Peter A.; Behrens, Annika; Cadby, Gemma; Murphy, Rachel Anne; Aronson, Kristan; Howell, Anthony; Astley, Susan; Couch, Fergus; Olson, Janet; Milne, Roger L.; Giles, Graham G.; Haiman, Christopher A.; Maskarinec, Gertraud; Winham, Stacey; John, Esther M.; Kurian, Allison; Eliassen, Heather; Andrulis, Irene L.; Evans, D. G.; Newman, William G.; Hall, Per; Czene, Kamila; Swerdlow, Anthony; Jones, Michael; Pollan, Marina; Fernandez-Navarro, Pablo; McConnell, Daniel S.; Kristensen, Vessela N.; Rothstein, Joseph H.; Wang, Pei; Habel, Laurel A.; Sieh, Weiva; Dunning, Alison M.; Pharoah, Paul D. P.; Easton, Douglas F.; Gierach, Gretchen L.; Tamimi, Rulla M.; Vachon, Celine M.; Lindström, Sara

Abstract

Background Mammographic density (MD) phenotypes, including percent density (PMD), area of dense tissue (DA), and area of non-dense tissue (NDA), are associated with breast cancer risk. Twin studies suggest that MD phenotypes are highly heritable. However, only a small proportion of their variance is explained by identified genetic variants. Methods We conducted a genome-wide association study, as well as a transcriptome-wide association study (TWAS), of age- and BMI-adjusted DA, NDA, and PMD in up to 27,900 European-ancestry women from the MODE/BCAC consortia. Results We identified 28 genome-wide significant loci for MD phenotypes, including nine novel signals (5q11.2, 5q14.1, 5q31.1, 5q33.3, 5q35.1, 7p11.2, 8q24.13, 12p11.2, 16q12.2). Further, 45% of all known breast cancer SNPs were associated with at least one MD phenotype at p 

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Title
Genome-wide and transcriptome-wide association studies of mammographic density phenotypes reveal novel loci
Creator
Chen, Hongjie; Fan, Shaoqi; Stone, Jennifer; Thompson, Deborah J.; Douglas, Julie; Li, Shuai; Scott, Christopher; Bolla, Manjeet K.; Wang, Qin; Dennis, Joe; Michailidou, Kyriaki; Li, Christopher; Peters, Ulrike; Hopper, John L.; Southey, Melissa C.; Nguyen-Dumont, Tu; Nguyen, Tuong L.; Fasching, Peter A.; Behrens, Annika; Cadby, Gemma; Murphy, Rachel Anne; Aronson, Kristan; Howell, Anthony; Astley, Susan; Couch, Fergus; Olson, Janet; Milne, Roger L.; Giles, Graham G.; Haiman, Christopher A.; Maskarinec, Gertraud; Winham, Stacey; John, Esther M.; Kurian, Allison; Eliassen, Heather; Andrulis, Irene L.; Evans, D. G.; Newman, William G.; Hall, Per; Czene, Kamila; Swerdlow, Anthony; Jones, Michael; Pollan, Marina; Fernandez-Navarro, Pablo; McConnell, Daniel S.; Kristensen, Vessela N.; Rothstein, Joseph H.; Wang, Pei; Habel, Laurel A.; Sieh, Weiva; Dunning, Alison M.; Pharoah, Paul D. P.; Easton, Douglas F.; Gierach, Gretchen L.; Tamimi, Rulla M.; Vachon, Celine M.; Lindström, Sara
Contributor
BC Cancer Agency
Publisher
BioMed Central
Date Issued
2022-04-12
Description
Background Mammographic density (MD) phenotypes, including percent density (PMD), area of dense tissue (DA), and area of non-dense tissue (NDA), are associated with breast cancer risk. Twin studies suggest that MD phenotypes are highly heritable. However, only a small proportion of their variance is explained by identified genetic variants. Methods We conducted a genome-wide association study, as well as a transcriptome-wide association study (TWAS), of age- and BMI-adjusted DA, NDA, and PMD in up to 27,900 European-ancestry women from the MODE/BCAC consortia. Results We identified 28 genome-wide significant loci for MD phenotypes, including nine novel signals (5q11.2, 5q14.1, 5q31.1, 5q33.3, 5q35.1, 7p11.2, 8q24.13, 12p11.2, 16q12.2). Further, 45% of all known breast cancer SNPs were associated with at least one MD phenotype at p 
Subject
Mammographic density; Breast cancer; Genome-wide association study (GWAS); Transcriptome-wide association study (TWAS)
Genre
Article
Type
Text
Language
eng
Date Available
2022-05-31
Provider
Vancouver : University of British Columbia Library
Rights
Attribution 4.0 International (CC BY 4.0)
DOI
10.14288/1.0413720
URI
http://hdl.handle.net/2429/81667
Affiliation
Medicine, Faculty of; Non UBC; Population and Public Health (SPPH), School of
Citation
Breast Cancer Research. 2022 Apr 12;24(1):27
Publisher DOI
10.1186/s13058-022-01524-0
Peer Review Status
Reviewed
Scholarly Level
Faculty; Researcher
Copyright Holder
The Author(s)
Rights URI
http://creativecommons.org/licenses/by/4.0/
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Attribution 4.0 International (CC BY 4.0)