Bio-Social Pathways Linking Socioeconomic Adversity to Obesity

将社会经济逆境与肥胖联系起来的生物社会途径

• 批准号: 10732033
• 负责人: Lindsay Fernandez-Rhodes
• 金额: $ 12.47万
• 依托单位: PENNSYLVANIA STATE UNIVERSITY, THE
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-08-17 至 2025-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10732033
• 关键词: Adult; Affect; African American; African American population; Atherosclerosis Risk in Communities; Biological; Biological Process; Biology; Biosocial; Body mass index; Cardiovascular Diseases; Central obesity; Classification; Clinical; Cohort Studies; Complex; Cytosine; DNA Methylation; Data; Data Analyses; Disease Outcome; Disparity; Dyslipidemias; Economic Burden; Education; Environment; Epidemiology; Epigenetic Process; Ethnic Origin; Ethnic Population; Etiology; European; Event; Functional disorder; Funding; Gene Expression; Genes; Genetic; Genetic Variation; Genomics; Grant; Guanine; Health Disparities Research; Heterogeneity; Hispanic; Impairment; Income; Individual; Inflammation; Intervention; Investigation; Jackson Heart Study; Japanese American; Latino; Learning; Life; Life Cycle Stages; Life Experience; Link; Measures; Mediating; Metabolic; Methylation; Minority; Modeling; National Heart, Lung, and Blood Institute; Native Hawaiian; Obesity; Obesity Epidemic; Occupational Status; Occupations; Pathway interactions; Phenotype; Population; Population Heterogeneity; Prevalence; Public Health; Race; Reporting; Research; Research Proposals; Risk; Risk Factors; Role; Sampling; Shapes; Site; Skin; Socioeconomic Status; Source; Surveys; Techniques; Testing; Time; Translating; United States National Institutes of Health; Women' s Health; Work; adult obesity; blood pressure elevation; burden of illness; cardiometabolism; cardiovascular disorder risk; cohort; disease disparity; disorder risk; epigenomics; ethnic disparity; ethnic diversity; ethnic minority; experience; health disparity; improved; innovation; inorganic phosphate; multi-ethnic; new therapeutic target; novel; novel marker; obesity risk; pharmacologic; population health; racial disparity; racial diversity; racial minority; racial population; sex; social; social determinants; socioeconomic adversity; socioeconomics; study population

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.

项目概要 过去 40 年来，美国肥胖患病率显着上升——成年人中肥胖率增加了一倍 并对少数种族/族裔产生不成比例的影响。这增加了临床、社会和经济 公众尤其是少数族裔的心血管疾病（CVD）负担。 CVD及其前身 危险因素（即肥胖、血脂异常、炎症、血压升高）也显示出显着差异 处于危险之中。例如，肥胖风险因社会经济地位、社会经济地位（SES）而异，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到底是如何转化为生物学上的逆境的。 导致更大疾病负担的变化。表观遗传学提供了一个框架来测试不利的程度 环境和生活经历改变生物过程并影响疾病风险。我们的研究将利用 约 9,000 名祖先不同的个体，四个由 NIH 资助的种族/族裔多元化的大型队列： 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 利用现有数据进行研究，测试 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发现 差异DNA甲基化与一些肥胖相关的社会经济逆境的组成部分相关 基因，为我们的创新假设提供强有力和令人信服的支持。在此，我们提出一个 使用综合得分对五个种族/民族的现有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 调节社会经济逆境与肥胖之间的关联，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来模拟 SES、肥胖和最终 CVD 之间的路径 结果。该资助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）如何因人而异 种族/族裔群体造成 CVD 差异。我们的研究具有创新性，因为它是前所未有的 对祖先多样化样本进行调查、检查和 DNA 甲基化分型的整合。这 该项目的预期结果将提高我们对肥胖和心血管疾病的机制理解，以及我们的 能够识别不同领域针对 CVD 的潜在可行的公共卫生或药物干预措施 人口。