Social Stressors, Epigenetics and Health Status in Underrepresented minorities

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SUMMARY Type 2 Diabetes (T2D) is one of the fastest-growing chronic diseases globally and causes disability, amplified healthcare costs, and mortality. T2D disproportionately afflicts ethnic minorities in the United States (US). Puerto Ricans (PR) have among the highest T2D rates in the U.S. While unhealthy lifestyle behaviors are known contributors to this disparity, the sociocultural environment of PR may be an equally important and understudied component of the excess T2D. Here, we introduce two cohorts: The Boston Puerto Rican Health Study (BPRHS) and Puerto Rico Observational Study of Psychosocial, Environmental, and Chronic Disease Trends (PROSPECT) as complementary cohorts of adults living in the northeast US (MPR) and Puerto Rico (IPR), providing a unique opportunity to understand T2D-related disparities in an at-risk group with different social and environmental settings. Evidence suggests that social factors affect health via epigenomic modifications. However, the related biological pathways are unknown. The study of epigenomic variation within minority populations exposed to different adverse and protective social factors offers a unique opportunity to characterize how environmental exposures and other social stressors interact with genes to influence T2D risk. Our central hypotheses are that 1) MPR are exposed to more adverse social factors and live in less protective social environments than IPR, and 2) this results in DNA methylation (DNAm) profiles consistent with higher T2D risk. We will test these hypotheses in cross-sectional and longitudinal analyses via the following aims: (1) To determine variations in DNAm and their association with T2D prevalence, incidence, and metabolic biomarkers known to contribute to T2D burden in MPR vs. IPR. To achieve this goal and subsequent aims, we will measure ~850K DNAm in paired BPRHS blood samples (n=600 visit (v)1 and n=600 v3) and 600 samples from PROSPECT (v1). (2) To characterize cross-sectional and longitudinal associations between genome-wide DNAm and specific social stressors (i.e., adverse childhood or life events, discrimination), and protective social factors (i.e., social support, coping, resiliency, community connection), along with behavioral factors (healthy diet, physical activity and adequate sleep); and to describe their relationships with metabolic and physiological pathways relevant to risk and control of T2D. (3) To quantify associations between social and behavioral stressors and biological age acceleration in the BPRHS (V1 and V3; ~6 y follow-up) and PROSPECT (V1) cohorts, using DNAm data from Aim 1. Defining mechanisms by which DNAm modifications and associated pathways relate to T2D risk will support the development of innovative strategies in public health to cope with environmental and social stressors to subsequently prevent T2D and related health disparities in vulnerable populations. This proposal will leverage and expand existing resources and established collaborative expertise.