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Gladish, Nicole

University of British Columbia

Interpersonal and societal adversity experienced throughout life, such as abuse or low socio-economic status (SES), have been associated with negative health outcomes. Many of these diseases share the common thread of inflammation, inspiring the hypothesis that chronic stress resulting from adverse experiences over activates the hypothalamic-pituitary- adrenal (HPA) axis resulting in dysregulation of the immune system. DNA methylation (DNAm), a methyl group covalently bound to cytosine bases for the purposes of this thesis, is one of many epigenetic mechanisms involved in responding to environmental signals in the genomic context. As such, this modification may be particularly pertinent to understanding how adverse experiences can become embedded in a way that results in lifelong health disparities. The overarching aim of this dissertation is to understand how various measures of adversity throughout the life-course could associate with DNAm differences between individuals. Initially, I compared whole blood DNAm patterns amongst elderly individuals with different years of education, household assets and self-reported measures of economic standing in childhood and older adulthood, in addition to a composite socioeconomic (SES) measure. I found there were significantly more DNAm associations with older adulthood relative to retrospective childhood SES measures, and the subjective SES measures displayed a dampened signal relative to objective ones. Next, I investigated the relationship between the inflammatory biomarker serum IL-6, lifetime SES measures and purified monocyte DNAm patterns amongst adults. Here, I found the relationship between some CpGs and IL-6 was partially explained by SES. Additionally, differences in SES-associated DNAm sites were seen predominantly amongst individuals who experienced low early life and high adulthood SES. Finally, I investigated how childhood abuse associated with DNAm in spermatozoa of adult men. Though this was a small pilot study, I found a subset of differentially methylated regions associated with childhood abuse. These associations were stable over a two-month period and survived adjusting for current life adversity measures. Overall, these findings provide evidence that the tissue, timing, and measure of adversity experienced are important considerations for social epigenetic studies and can yield unique DNAm patterns in a context-specific way.

Text

2022-09-30

Attribution-NonCommercial-NoDerivatives 4.0 International

http://hdl.handle.net/2429/79623

Medical Genetics

University of British Columbia

UBCV

http://creativecommons.org/licenses/by-nc-nd/4.0/