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.

项目摘要 在过去的40年中，美国的肥胖症患病率显着增加 - 成年人的两倍 并不成比例地影响种族/族裔少数民族。这增加了临床，社会和经济 心血管疾病的负担（CVD）给公众，尤其是少数民族的负担。 CVD及其先例 危险因素（即肥胖，血脂异常，炎症，血压升高）也显示出明显的分布 风险。例如，观察风险因社会经济地位而异，即教育程度，收入，收入， 占据地位；然而，目前尚不清楚如何将社会经济冒险转化为生物学 导致疾病更大的变化。表观遗传学提供了一个测试对手的框架 环境和生活经历改变了生物学过程并影响疾病的风险。我们的研究将利用 〜9,000个祖先多样化的个人四个大型种族/种族多样性的NIH资助人群：动脉粥样硬化 社区（ARIC），妇女健康倡议，杰克逊心脏研究和多民族队列的风险 使用现有数据研究以测试DNA甲基化是否是一种生物学机制，SES导致肥胖 和下游心脏代谢功能障碍。我们在ARIC非裔美国人中进行的初步分析已确定 差异DNA甲基化与几个与肥胖有关的社会经济广告的组成部分相关 基因，对我们创新的假设提供了强有力而令人信服的支持。在这里，我们提出了一个 使用复合分数的五个种族/族裔群体的额外甲基化数据的全面分析 SES以及多种肥胖度量。我们的两个具体目标将：1）确定DNA甲基化位点 调解社会经济广告与肥胖之间的关联，与局部遗传变异无关； 2）整合了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 结果。这种赠款机制的资金将使我们能够描述DNA甲基化位点是 与SES和/或肥胖相关，以及这些变化（或它们与SES的相互作用）如何变化 种族/种族群体有助于CVD差异。由于其前所未有的研究，我们的研究具有创新性 在祖先多样化的样本上的调查，检查和DNA甲基化型的整合。这 项目的预期发现将改善我们对肥胖和CVD的机械理解，以及我们的 能够识别潜水员中CVD的潜在可靠公共卫生或药物干预措施 人群。