Bio-Social Pathways Linking Socioeconomic Adversity to Obesity

项目总结 在过去的40年里，美国的肥胖率显著增加--成年人的肥胖率翻了一番 而且对种族/少数民族的影响不成比例。这增加了临床、社会和经济方面的 心血管疾病(CVD)对公众造成负担，对少数群体尤其如此。心血管疾病及其前驱疾病 危险因素(如肥胖、血脂异常、炎症、血压升高)也表现出显著的差异。 冒着风险。例如，肥胖风险因社会经济地位、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 导致更大疾病负担的变化。表观遗传学为测试不利程度提供了一个框架 环境和生活经历改变了生物过程，形成了疾病风险。我们的研究将利用 ~9,000名祖籍不同的人NIH资助的四大种族/民族不同的队列：动脉粥样硬化 和社区风险(ARIC)、妇女健康倡议、杰克逊心脏研究和多种族队列 利用现有数据研究DNA甲基化是否是SES导致肥胖的生物机制 和下游心脏代谢功能障碍。我们在ARIC非裔美国人中的初步分析发现 与肥胖相关的几个社会经济逆境因素相关的差异DNA甲基化 基因，为我们的创新假设提供了强有力和令人信服的支持。在此，我们提出一种 综合分析来自五个种族/民族的现有甲基化数据 SES以及多项肥胖指标。我们的两个具体目标将：1)识别DNA甲基化位点 调节社会经济逆境和肥胖之间的联系，不受当地遗传变异的影响； 2)整合所有可用的生物-社会数据，以模拟SES、肥胖和最终心血管疾病之间的路径 结果。来自这一赠款机制的资金将使我们能够描述DNA甲基化位点的程度 与SES和/或肥胖相关，以及这些变化(或它们与SES的相互作用)在不同阶段的变化情况 种族/族裔群体造成心血管疾病的差异。我们的研究是创新的，因为它是前所未有的 整合调查、检查和DNA甲基化--对不同祖先的样本进行分型。这 该项目的预期发现将改善我们对肥胖和心血管疾病的机械理解，以及我们的 能够确定对不同类型的心血管疾病可能采取的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.