Social Stressors, Epigenetics and Health Status in Underrepresented minorities

总结 2型糖尿病（T2 D）是全球增长最快的慢性疾病之一， 医疗费用和死亡率。T2 D不成比例地折磨着美国的少数族裔。 波多黎各人（PR）是美国T2 D发病率最高的人之一，而不健康的生活方式行为 众所周知，这种差异的贡献者，公关的社会文化环境可能是一个同样重要的， 过度T2 D的未充分研究的成分。在这里，我们介绍两个队列：波士顿波多黎各健康 研究（BPRHS）和波多黎各的社会心理、环境和慢性疾病的观察性研究 趋势（前景）作为美国东北部（MPR）和波多黎各成年人的补充队列 (IPR)，提供了一个独特的机会，以了解T2 D相关的差异，在一个风险群体与不同的 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，相关的生物学途径是未知的。表观基因组变异的研究 面临各种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如何与基因相互作用，以影响T2 D风险。 我们的中心假设是：1）MPR暴露于更多不利的社会因素，生活在保护性较低的环境中 社会环境比IPR，2）这导致DNA甲基化（DNAm）谱与更高的 T2 D风险。我们将通过横向和纵向分析来检验这些假设，目的如下：（1） 确定DNAm的变化及其与T2 D患病率、发病率和代谢的相关性 已知有助于MPR与IPR中T2 D负荷的生物标志物。为了实现这一目标和后续目标，我们 将在配对的BPRHS血液样本（n=600次访视（v）1和n=600次v3）和600份样本中测量约850 K DNAm 前景（v1）(2)为了描述全基因组之间的横向和纵向关联， DNA m和特定的社会压力源（即，不利的童年或生活事件，歧视）和保护性社会 因素（即，社会支持，应对，弹性，社区联系），沿着行为因素（健康 饮食、体力活动和充足的睡眠）;并描述它们与代谢和生理 与T2 D风险和控制相关的途径。(3)为了量化社会和行为之间的联系， BPRHS（V1和V3;约6年随访）和前景（V1）中的应激源和生物学年龄加速 队列，使用来自Aim 1的DNAm数据。定义DNA修饰和相关的 与T2 D风险相关的途径将支持公共卫生创新战略的发展， 环境和社会压力因素，以随后防止T2 D和相关的健康差距， 人口。这项提议将利用和扩大现有资源和已建立的协作专门知识。

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.