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: 10701077
• 负责人: Lifang Hou
• 金额: $ 52.94万
• 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/10701077
• 关键词: Address; Adult; Affect; Age; Aging; Biological; Biological Markers; Black race; Cardiovascular Diseases; Cardiovascular system; Cause of Death; Censuses; 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; Disparity; 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; 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; Testing; Time; Trans-Omics for Precision Medicine; Variant; Visualization; 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 disparity; racial minority population; social; social disparities; 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，并且对黑人的影响尤为严重 在美国社区，迫切需要解决心血管种族差异。个人级别 健康的社会决定因素（iSDH；例如贫困和教育）和社区层面的 SDH (nSDH) 与 CVD 危险因素以及亚临床和临床结果有关。接触 SDH 可能开始于 年轻时并在一生中积累。然而，大多数关于 SDH 和 CVD 的研究都集中在其中一个 老年人或老年人，而种族差异研究则侧重于自我报告的种族。纵向研究 迫切需要从年轻时开始就 SDH 进行研究，同时考虑遗传血统与 CVD 种族差异的关系。 此外，目前衡量 SDH 的指数没有考虑具体的健康结果，因此无法提供 有关这些结果的信息有限。 SDH 和 CVD 之间的潜在生物学机制仍然存在 很大程度上不为人知。表观遗传标记与社会劣势和心血管疾病结果相关，并且 表观遗传过程代表了 SDH 和 CVD 种族差异之间的潜在生物调节因素。然而， 大多数先前的研究都是横断面的，仅限于一两个时间点和/或使用之后收集的样本 疾病的发展。这些限制阻碍了我们研究表观基因组生物标志物的动态性质 以及它们对中年 SDH 暴露到亚临床 CVD 过程的时间和/或中介作用， 然后在晚年进入临床心血管疾病。在拟议的研究中，我们使用社会表观遗传学来解决这些差距 了解个人和社区水平 SDH 对 DNA 甲基化标记影响的方法 以及 SDH 相关 DNA 甲基化标记在 CVD 发展和差异中的中介/时间作用。 我们为开展这项研究做好了独特的准备，因为我们可以利用冠状动脉的现有资源 年轻人动脉风险发展 (CARDIA) 研究。 CARDIA 是一个基于社区的混血儿队列 来自美国四个大城市的 18-30 岁个体，社会劣势差异较大， 目前每 5 年进行一次随访，持续时间 > 35 年。具体来说，我们建议 (1) 开发 iSDH 和 nSDH 指数， 以及亚临床 CVD 特有的轨迹； (2) 鉴定 SDH 相关 DNAm 生物标志物并检查其 使用 TOPMed 即用型纵向表观基因组数据确定 CVD 风险和差异中的作用； (3)检查遗传 使用 TOPMed 即用型研究 SDH 相关 DNAm 生物标志物与 CVD 风险和差异相关的作用 全基因组测序数据； (4) 在其他 TOPMed 队列中验证我们的发现，并部署用户友好的 Web 应用程序。 通过评估与 SDH 相关的多种可改变的 CVD 风险因素，这一高度耗时和成本的研究结果 有效的研究对于针对高需求人群、针对个人和个体制定干预措施具有不可估量的价值。 社区层面，并分配资源以解决美国和世界各地的社会劣势问题。

项目成果

Social Determinants, Cardiovascular Disease, and Health Care Cost: A Nationwide Study in the United States Using Machine Learning.

• DOI: 10.1161/jaha.122.027919
• 发表时间: 2023-03-07
• 期刊: JOURNAL OF THE AMERICAN HEART ASSOCIATION
• 影响因子: 5.4
• 作者: Sun, Feinuo;Yao, Jie;Du, Shichao;Qian, Feng;Appleton, Allison A.;Tao, Cui;Xu, Hua;Liu, Lei;Dai, Qi;Joyce, Brian T.;Nannini, Drew R.;Hou, Lifang;Zhang, Kai
• 通讯作者: Zhang, Kai