Epigenomic landscape of individual- and neighborhood-level social disadvantages and cardiovascular health disparity

个人和社区层面的社会劣势和心血管健康差异的表观基因组景观

• 批准号: 10531486
• 负责人: Lifang Hou
• 金额: $ 56.95万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-15 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10531486
• 关键词: Address; Adult; Affect; Age; Aging; Biological; Biological Markers; Black race; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Censuses; Centers for Disease Control and Prevention (U.S.); Characteristics; Childhood; Cities; Clinical; Communities; Computer software; Coronary Artery Risk Development in Young Adults Study; Cost of Illness; Crime; Cross-Sectional Studies; DNA; DNA Methylation; Data; Development; Disease; Disease Outcome; Economic Factors; Education; Elderly; Enrollment; Environmental Risk Factor; Epigenetic Process; Exposure to; Funding; Gene Expression; Genetic; Health; Health Personnel; Health care facility; High Prevalence; Individual; Intervention; Investigation; Knowledge; Life; Life Cycle Stages; Link; Longevity; Longitudinal Studies; Measures; Mediating; Mediation; Mediator of activation protein; Methods; Methylation; Modification; Molecular Target; National Heart, Lung, and Blood Institute; Nature; Neighborhoods; Outcome; Participant; Patient Self-Report; Physical activity; Physicians; Play; Population; Poverty; Process; Quantitative Trait Loci; Race; Research Personnel; Resources; Risk; Risk Factors; Role; Sampling; Socioeconomic Status; Supervision; Testing; Time; Trans-Omics for Precision Medicine; Variant; base; biracial; cardiovascular disorder prevention; cardiovascular disorder risk; cardiovascular health; cardiovascular risk factor; clinical development; cohort; coronary artery calcification; cost; cost effective; dimensional analysis; disease disparity; epigenetic marker; epigenomics; ethnic minority population; genome sequencing; genomic data; health disparity; high dimensionality; indexing; longitudinal database; member; methylation biomarker; middle age; modifiable risk; novel; prediction algorithm; racial and ethnic; racial disparity; social; social disadvantage; social factors; social health determinants; social vulnerability; user-friendly; web app; web interface; whole genome

ABSTRACT As cardiovascular disease (CVD) remains the leading cause of death and disproportionately affects Black communities in the U.S., there is an urgent need to address cardiovascular racial disparities. Individual-level social determinants of health (iSDH; e.g., poverty and education) and neighborhood-level SDH (nSDH) have been linked to CVD risk factors, as well as subclinical and clinical outcomes. Exposure to SDH may start from young age and accumulate over the lifespan. However, most studies on SDH and CVD have focused on either older adults or the elderly, while racial disparity studies have focused on self-reported race. Longitudinal studies of SDH from young age that also consider genetic ancestry in relation to CVD racial disparity are urgently needed. Furthermore, current indices to measure SDH do not take specific health outcomes into account and thus provide limited information for these outcomes. The underlying biological mechanisms between SDH and CVD remain largely unknown. Epigenetic markers have been associated with social disadvantages and CVD outcomes, and epigenetic processes represent a potential biological mediator between SDH and CVD racial disparity. However, most prior studies are cross-sectional and limited to one or two time points and/or use samples collected after disease development. These limitations hinder us from studying the dynamic nature of epigenomic biomarkers and their temporal and/or mediating role on the process from SDH exposure to subclinical CVD at middle age, and then into clinical CVD later in life. In the proposed study, we address these gaps using a social epigenetic approach to understand the impact of the individual- and neighborhood-level SDH on DNA methylation markers and the mediating/temporal role of SDH-associated DNA methylation markers in CVD development and disparity. We are uniquely poised to conduct this study because we can leverage existing resources from the Coronary Artery Risk Development in Young Adults (CARDIA) Study. CARDIA is a community-based biracial cohort of individuals enrolled at ages 18–30 years from four large U.S. cities with large variations in social disadvantages, currently followed every 5 years for >35 years. Specifically, we propose (1) to develop iSDH and nSDH indices, and trajectories specific to subclinical CVD; (2) to identify SDH-associated DNAm biomarkers and examine their roles in CVD risk and disparity using TOPMed ready-to-use longitudinal epigenomic data; (3) to examine genetic roles in SDH-associated DNAm biomarkers in relation to CVD risk and disparity using TOPMed ready-to-use WGS data; and (4) to validate our findings in other TOPMed cohorts, and deploy a user-friendly web application. By evaluating multiple modifiable risk factors of CVD related to SDH, the findings from this highly time- and cost- effective study will be invaluable for targeting high-need populations, tailoring interventions at the individual and neighborhood levels, and distributing resources to tackle social disadvantages in the U.S. and worldwide.

抽象的 由于心血管疾病（CVD）仍然是死亡的主要原因，而无能为力影响黑色 在美国的社区，迫切需要添加以添加以添加以添加。 卫生的社会决定因素（ISDH；例如，贫困和教育）和邻居级别的SDH（NSDH） 与CVD风险因素以及亚临床和临床结果有关。 但是，年龄和积累了寿命。 老年人或老年人，虽然差异集中在自我报告的种族上 迫切需要急需考虑与CVD种族相关的遗传血统的SDH的SDH。 此外，当前测量SDH的指标不考虑特定的健康结果，因此提供了 结果有限的信息。 在很大程度上未知。 表观遗传过程代表了SDH和CVD种族差异之间的潜在生物介体。 大多数先前的研究都是横截面，限于一个或两个时间点和/或使用后收集的样品 疾病的发展。 以及他们在中期SDH暴露于临床CVD的过程中的时间和/或中介作用， 在临床的临床中，我们的生活中的研究中，我们使用社会表观遗传来解决这些差距 了解个体和邻里级别SDH对DNA甲基化标记的影响的方法 以及与SDH相关的DNA甲基化标志物在CVD发展和差异中的介导/时间作用。 我们独一无二地进行研究研究研究，我们可以利用冠状动脉的现有巨额 年轻人的动脉风险发展（Cardia）研究是基于共同的混血儿队 从四个大型美国城市中招收18至30岁的个人，社会劣势差异很大， 目前每5年遵循> 35年。 和特定于亚临床CVD的轨迹； CVD风险和差异中的角色，使用现成的纵向基依赖氏症数据；（3）检查遗传 与CVD风险和差异相关的SDH相关DNAM生物标志物中的角色 WGS数据； 通过评估与SDH相关的CVD的可修改风险因素 有效的研究对于针对高必要的受欢迎程度，对个人定制干预措施以及 邻里水平，并分发资源以解决美国和世界各地的袜子袜子的缺点。