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

基本信息

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
项目类别：
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&apos 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

项目摘要

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这增加了临床、社会和经济方面的影响。心血管疾病（CVD）对公众，尤其是少数族裔的负担。危险因素（即肥胖、血脂异常、炎症、血压升高）也显示出显着差异例如，肥胖风险因社会经济地位、SES（即教育程度、收入）而异。职业地位；然而，尚不清楚社会经济逆境究竟如何转化为生物地位导致更大疾病负担的变化提供了一个框架来测试不利程度。环境和生活经历会改变生物过程并影响疾病风险。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我们对 ARIC 非洲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。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 以及多种肥胖测量方法将：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 之间的路径该资助机制的资助将使我们能够描述 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）如何因人而异我们的研究具有前所未有的创新性。对祖先多样化样本进行调查、检查和 DNA 甲基化分型的整合。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。