Social Stressors, Epigenetics and Health Status in Underrepresented minorities

代表性不足的少数群体的社会压力源、表观遗传学和健康状况

• 批准号: 10707995
• 负责人: Jose M. Ordovas
• 金额: $ 54.22万
• 依托单位: TUFTS UNIVERSITY BOSTON
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-21 至 2027-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10707995
• 关键词: Acceleration; Accounting; Adult; Adverse event; Affect; Age; Automobile Driving; Behavior; Behavioral; Biological; Biological Aging; Biological Markers; Biology; Blood specimen; Boston; Characteristics; Childhood; Chronic Disease; Chronology; Communities; Cross-Sectional Studies; DNA; DNA Methylation; Data; Development; Diet; Discrimination; Disparity; Environment; Environmental Exposure; Epigenetic Process; Event; Exposure to; Family member; Gene Expression; Genes; Glucose; Glycosylated hemoglobin A; Goals; Health; Health Care Costs; Health Status; Hispanic Populations; Incidence; Individual; Island; Knowledge; Life; Location; Massachusetts; Measures; Mediator; Metabolic; Minority Groups; Modification; Non-Insulin-Dependent Diabetes Mellitus; Not Hispanic or Latino; Observational Study; Participant; Pathway interactions; Physical activity; Physiological; Populations at Risk; Prevalence; Productivity; Psychosocial Assessment and Care; Public Health; Puerto Rican; Puerto Rico; Research; Resources; Risk; Sampling; Social Environment; Social support; Standardization; Testing; Time; Underrepresented Minority; Unhealthy Diet; United States; Variant; Visit; Vulnerable Populations; adequate sleep; cohort; coping; diabetes risk; disability; environmental stressor; epigenomics; ethnic minority; family support; follow-up; genome-wide; good diet; health disparity; high risk; innovation; longitudinal analysis; metabolic profile; methylome; migration; mortality; prevent; protective factors; recruit; resilience; response; social; social culture; social disparities; social factors; social stressor; stressor; trend; unhealthy lifestyle

SUMMARY Type 2 Diabetes (T2D) is one of the fastest-growing chronic diseases globally and causes disability, amplified healthcare costs, and mortality. T2D disproportionately afflicts ethnic minorities in the United States (US). Puerto Ricans (PR) have among the highest T2D rates in the U.S. While unhealthy lifestyle behaviors are known contributors to this disparity, the sociocultural environment of PR may be an equally important and understudied component of the excess T2D. Here, we introduce two cohorts: The Boston Puerto Rican Health Study (BPRHS) and Puerto Rico Observational Study of Psychosocial, Environmental, and Chronic Disease Trends (PROSPECT) as complementary cohorts of adults living in the northeast US (MPR) and Puerto Rico (IPR), providing a unique opportunity to understand T2D-related disparities in an at-risk group with different social and environmental settings. Evidence suggests that social factors affect health via epigenomic modifications. However, the related biological pathways are unknown. The study of epigenomic variation within minority populations exposed to different adverse and protective social factors offers a unique opportunity to characterize how environmental exposures and other social stressors interact with genes to influence T2D risk. Our central hypotheses are that 1) MPR are exposed to more adverse social factors and live in less protective social environments than IPR, and 2) this results in DNA methylation (DNAm) profiles consistent with higher T2D risk. We will test these hypotheses in cross-sectional and longitudinal analyses via the following aims: (1) To determine variations in DNAm and their association with T2D prevalence, incidence, and metabolic biomarkers known to contribute to T2D burden in MPR vs. IPR. To achieve this goal and subsequent aims, we will measure ~850K DNAm in paired BPRHS blood samples (n=600 visit (v)1 and n=600 v3) and 600 samples from PROSPECT (v1). (2) To characterize cross-sectional and longitudinal associations between genome-wide DNAm and specific social stressors (i.e., adverse childhood or life events, discrimination), and protective social factors (i.e., social support, coping, resiliency, community connection), along with behavioral factors (healthy diet, physical activity and adequate sleep); and to describe their relationships with metabolic and physiological pathways relevant to risk and control of T2D. (3) To quantify associations between social and behavioral stressors and biological age acceleration in the BPRHS (V1 and V3; ~6 y follow-up) and PROSPECT (V1) cohorts, using DNAm data from Aim 1. Defining mechanisms by which DNAm modifications and associated pathways relate to T2D risk will support the development of innovative strategies in public health to cope with environmental and social stressors to subsequently prevent T2D and related health disparities in vulnerable populations. This proposal will leverage and expand existing resources and established collaborative expertise.

概括 2型糖尿病（T2D）是全球增长最快的慢性疾病之一，引起残疾，放大 医疗保健成本和死亡率。 T2D在美国（美国）遭受了少数民族的不成比例。 波多黎各人（PR）在美国的T2D率最高，而不健康的生活方式行为是 这一差异的已知贡献者，公关的社会文化环境可能同样重要，并且 多余的T2D的研究成分。在这里，我们介绍了两个队列：波士顿波多黎各人健康 研究（BPRH）和波多黎各的心理，环境和慢性疾病的观察性研究 趋势（前景）作为居住在美国东北部（MPR）和波多黎各的成年人的补充人群 （IPR），提供了一个独特的机会，可以在具有不同的危险中了解与T2D相关的差距 社会和环境环境。证据表明，社会因素通过表观基因组影响健康 修改。但是，相关的生物途径尚不清楚。研究表观基因组变异的研究 面临不同不利和保护性社会因素的少数民族人口为您提供了独特的机会 表征环境暴露和其他社会压力与基因相互作用以影响T2D风险的方式。 我们的核心假设是1）MPR暴露于更不利的社会因素，并以较少的保护性生活 社会环境比IPR，2）这导致DNA甲基化（DNAM）剖面与较高 T2D风险。我们将通过以下目的在横截面和纵向分析中检验这些假设：（1） 确定DNAM的变化及其与T2D患病率，发病率和代谢的关系 生物标志物已知会导致MPR与IPR的T2D负担。为了实现这一目标和随后的目标，我们 将在配对的BPRHS血液样本中测量〜850K DNAM（n = 600访问（v）1和n = 600 V3）和600个样品 来自前景（v1）。 （2）表征全基因组之间的横截面和纵向关联 DNAN和特定的社会压力源（即童年或生活事件，歧视）和保护性社会 因素（即社会支持，应对，弹性，社区联系）以及行为因素（健康 饮食，体育锻炼和足够的睡眠）；并描述他们与代谢和生理学的关系 与T2D风险和控制有关的途径。 （3）量化社会和行为之间的关联 BPRH的压力源和生物年龄加速度（V1和V3; 〜6 y随访）和前景（V1） 同类，使用来自AIM 1的DNAM数据。定义DNAM修改和相关的机制 与T2D风险有关的途径将支持开发公共卫生中的创新策略以应对 环境和社会压力源，以防止T2D及相关的健康差异 人群。该建议将利用和扩大现有资源并建立合作专业知识。