Bio-Social Pathways Linking Socioeconomic Adversity to Obesity

项目摘要 在过去的40年里，美国肥胖症的患病率显著上升，成年人中的肥胖率翻了一番 不成比例地影响种族/族裔少数群体。这增加了临床，社会和经济 心血管疾病（CVD）对公众的负担，特别是对少数民族。CVD及其前因 风险因素（即，肥胖、血脂异常、炎症、血压升高）也显示出显著的差异 处于危险之中例如，肥胖风险因社会经济地位，即受教育程度，收入， 职业地位;然而，目前还不清楚社会经济逆境是如何转化为生物 这些变化导致了更大的疾病负担。表观遗传学提供了一个框架，用于测试 环境和生活经历改变生物过程并形成疾病风险。我们的研究将利用 约9，000名血统不同的个体，四个大型种族/民族多样化的NIH资助的队列： 和社区风险（ARIC），妇女健康倡议，杰克逊心脏研究和多民族队列 利用现有数据研究DNA甲基化是否是SES导致肥胖的生物学机制 和下游心脏代谢功能障碍。我们对ARIC非裔美国人的初步分析表明， 差异DNA甲基化与社会经济逆境的组成部分在几个肥胖相关 基因，为我们的创新假设提供了强有力的支持。在此，我们提出一个 使用以下综合评分对来自五个种族/民族的现存甲基化数据进行综合分析： SES以及多种肥胖指标。我们的两个具体目标是：1）确定DNA甲基化位点， 调解社会经济逆境和肥胖之间的关联，独立于当地的遗传变异; 2）整合所有可用的生物社会数据，以模拟SES、肥胖和最终CVD之间的途径 成果。从这个资助机制中获得的资金将使我们能够描述DNA甲基化位点在多大程度上被 与SES和/或肥胖相关，以及这些变化（或它们与SES的相互作用）如何在不同的 种族/族裔群体导致心血管疾病差异。本研究具有创新性， 整合调查，检查，和DNA甲基化分型的祖先不同的样品。这 该项目的预期发现将提高我们对肥胖和心血管疾病的机械理解， 能够在不同的人群中识别可能可行的CVD公共卫生或药物干预措施， 人口。

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.