The Add Health Epigenome Resource: Life course stressors and epigenomic modifications in adulthood

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Abstract Disparities by race/ethnicity and socioeconomic status exist across a range of cardiometabolic and mental health outcomes in adulthood, and have been traced to exposure to psychosocial stressors across the life course. The discovery of the epigenome provides a remarkable opportunity to identify the pathways by which psychosocial exposures get into the body to produce inequalities in health and disease. However, a major limitation of extant research on life course exposures and epigenetic modifications has been a dearth of prospective social and contextual data collection. Indeed, the majority of existing social epigenomic studies focus on an exposure at a single life stage or rely on retrospective report of only a few indicators of early life socioeconomic status. To more fully understand the ways in which psychosocial stressors influence the epigenome, it is paramount to connect rich longitudinal data on psychosocial stressors with epigenetic data and markers of health and disease. Our proposed research will examine “allostatic load”-related gene DNA methylation (DNAm) and expression relevant to life course psychosocial stressors, among participants in the National Longitudinal Study of Adolescent to Adult Health (Add Health). Specifically, our proposal seeks to uncover the impact of life course psychosocial stressors on functional epigenomic alterations, and to identify the epigenomic bridges that link psychosocial stressors with the emergence of poor mental health and cardiometabolic conditions in the US population. We hypothesize that exposure to psychosocial stressors across the life course, will be associated with allostatic load-related gene DNAm, and that these patterns will vary significantly by race/ethnicity and sex. Moreover, we hypothesize that life course stress-related methylation differences will be associated with cardiometabolic and mental health outcomes, and partially mediated by gene expression. We will test these hypotheses through the following specific aims: (1) Conduct DNAm testing and assess variation by age, race/ethnicity, sex, and SES among 4,200 Add Health participants; (2) Assess whether life course psychosocial stressors (e.g. socioeconomic adversity, trauma) are associated with DNAm in allostatic load genes among Add Health participants, including a subset of siblings and twins; and (3) Examine whether allostatic load gene DNAm is associated with cardiometabolic health and depression measures in adulthood. We will also assess whether these associations are mediated by gene expression. Overall, our proposal will provide an unprecedented epigenetic resource available to the global scientific community, and will identify novel pathways by which life course psychosocial stressors influence functional- and health relevant DNAm in the largest US nationally representative, racially/ethnically-diverse longitudinal study of social exposures on health.