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: 10523174
• 负责人: Jose M. Ordovas
• 金额: $ 56.72万
• 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/10523174
• 关键词: Acceleration; Accounting; Adult; Adverse event; Affect; Age; Automobile Driving; Behavior; Behavioral; Biological; Biological Aging; Biological Markers; Biology; Blood specimen; Boston; Centers for Disease Control and Prevention (U.S.); Characteristics; Childhood; Chronic Disease; Chronology; Communities; Cross-Sectional Studies; DNA; DNA Methylation; Data; Development; Diet; Discrimination; Environment; Environmental Exposure; Epigenetic Process; Event; Exposure to; Family member; Fibrinogen; Gene Expression; Genes; Glucose; Glycosylated hemoglobin A; Goals; Health; Health Care Costs; Health Status; Hispanic Populations; Incidence; Individual; Island; Knowledge; Lead; Life; Location; Massachusetts; Measures; Mediator of activation protein; Metabolic; Minority Groups; Modification; Non-Insulin-Dependent Diabetes Mellitus; Not Hispanic or Latino; Observational Study; Participant; Pathway interactions; Physical activity; Physiological; 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; base; 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 disadvantage; 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，会导致残疾、加剧 医疗费用和死亡率。在美国，T2D 严重影响着少数族裔。 波多黎各人 (PR) 是美国 T2D 发病率最高的人群之一。 除了造成这种差异的已知因素之外，公关的社会文化环境可能同样重要，而且 过量 T2D 的未充分研究的组成部分。在这里，我们介绍两个群体： 波士顿波多黎各健康中心 研究 (BPRHS) 和波多黎各社会心理、环境和慢性疾病观察研究 居住在美国东北部 (MPR) 和波多黎各的成年人的互补群体趋势 (PROSPECT) (IPR)，提供了一个独特的机会来了解具有不同疾病的高危人群中与 T2D 相关的差异。 社会和环境设置。有证据表明，社会因素通过表观基因组影响健康 修改。然而，相关的生物学途径尚不清楚。表观基因组变异的研究 暴露于不同不利和保护性社会因素的少数群体提供了独特的机会 描述环境暴露和其他社会压力因素如何与基因相互作用以影响 T2D 风险。 我们的中心假设是 1) MPR 暴露于更多不利的社会因素并且生活在保护较少的环境中 社会环境比 IPR 更重要，并且 2) 这导致 DNA 甲基化 (DNAm) 特征与更高的一致 T2D 风险。我们将通过横断面和纵向分析来检验这些假设，目的如下：(1) 确定 DNAm 的变异及其与 T2D 患病率、发病率和代谢的关系 MPR 与 IPR 中已知会导致 T2D 负担的生物标志物。为了实现这一目标和后续目标，我们 将测量配对 BPRHS 血液样本（n=600 次访问 (v)1 和 n=600 v3）和 600 个样本中的约 850K DNAm 来自前景 (v1)。 (2) 表征全基因组之间的横截面和纵向关联 DNAm 和特定的社会压力源（即不利的童年或生活事件、歧视）以及保护性社会 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、身体活动和充足的睡眠）；并描述它们与代谢和生理的关系 与 T2D 风险和控制相关的途径。 (3) 量化社会和行为之间的关联 BPRHS（V1 和 V3；约 6 年随访）和 PROSPECT (V1) 中的压力源和生物年龄加速 队列，使用目标 1 中的 DNAm 数据。定义 DNAm 修饰和关联的机制 与 T2D 风险相关的途径将支持公共卫生领域创新战略的制定，以应对 环境和社会压力源，以随后预防 T2D 和弱势群体的相关健康差异 人口。该提案将利用和扩展现有资源和已建立的协作专业知识。