Bio-Social Pathways Linking Socioeconomic Adversity to Obesity

项目总结

PROJECT SUMMARY Over the past 40 years, the prevalence of obesity has increased markedly in the US—doubling among adults and disproportionately affecting racial/ethnic minorities. This has increased the clinical, social and economic burden of cardiovascular disease (CVD) for the public, and especially so for minorities. CVD and its antecedent risk factors (i.e., obesity, dyslipidemia, inflammation, elevated blood pressure) also display notable disparities in risk. For example, obesity risk varies by socioeconomic status, SES, i.e. by educational attainment, income, occupational status; yet, it is unclear exactly how socioeconomic adversity is translated into the biologic changes that lead to greater disease burden. Epigenetics provides a framework for testing how adverse environments and life experiences change biologic processes and shape disease risk. Our study will leverage ~9,000 ancestrally diverse individuals four large racially/ethnically diverse NIH-funded cohorts: Atherosclerosis and Risk in Communities (ARIC), Women’s Health Initiative, Jackson Heart Study, and the Multi-Ethnic Cohort Study with existing data to test if DNA methylation is a biologic mechanism through which SES leads to obesity and downstream cardiometabolic dysfunction. Our preliminary analyses in ARIC African Americans identified differential DNA methylation associated with components of socioeconomic adversity at several obesity-related genes, lending strong and convincing support for our innovative hypotheses. Herein, we propose a comprehensive analysis of extant methylation data from five race/ethnic groups using a composite score of SES as well as multiple obesity measures. Our two specific aims will: 1) identify DNA methylation sites that mediate the association between socioeconomic adversity and obesity, independent of local genetic variation; and 2) integrate all available bio-social data to model the pathways between SES, obesity and ultimately CVD outcomes. Funding from this grant mechanism will allow us to describe extent that DNA methylation sites are associated with SES and/or obesity, and how these changes (or their interactions with SES) vary across race/ethnic groups to contribute to CVD disparities. Our study is innovative due to its unprecedented integration of survey, examination, and DNA methylation-typing on an ancestrally diverse sample. This project’s anticipated findings will improve both our mechanistic understanding of obesity and CVD, and our ability to identify potentially-actionable public health or pharmacologic interventions for CVD in diverse populations.