Social Stressors, Epigenetics and Health Status in Underrepresented minorities

摘要 2型糖尿病(T2D)是全球增长最快的慢性疾病之一，并导致残疾 医疗成本和死亡率。在美国，T2D对少数族裔的影响不成比例。 波多黎各人(PR)的T2D率在美国名列前茅，而不健康的生活方式行为 造成这种差异的已知因素，公关的社会文化环境可能是同样重要的 超额T2D的未被研究的组成部分。在这里，我们介绍两个队列：波士顿波多黎各健康 心理社会、环境和慢性病研究(BPRHS)和波多黎各观察性研究 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互补队列 (知识产权)，提供了一个独特的机会来了解不同风险群体中与T2D相关的差异 社会和环境环境。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 暴露在不同不利和保护性社会因素下的少数群体提供了一个独特的机会 描述环境暴露和其他社会应激源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暴露在更不利的社会因素中，生活在更不安全的环境中 社会环境，而不是知识产权，以及2)这导致DNA甲基化(DNaM)与更高的 T2D风险。我们将通过以下目标在横截面和纵向分析中检验这些假设：(1) 确定dNaM的变异及其与T2D患病率、发病率和代谢的关系 已知的生物标志物对MPR和IPR的T2D负担有贡献。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(n=600拜访(V)1和n=600 v3)和600个样本中测量~850K dNaM 来自Prospects(V1)。(2)描述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)和保护性社会 因素(即社会支持、应对、复原力、社区联系)，以及行为因素(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联系 BPRHS(V1和V3；~6岁随访)和展望(V1)的压力源和生物年龄加速 队列，使用来自目标1的dNaM数据。定义dNaM修改和关联的机制 与T2D风险相关的途径将支持制定公共卫生创新战略，以应对 环境和社会应激源，以随后预防T2D和相关的弱势人群健康差异 人口。这项提议将利用和扩大现有资源和既定的协作专业知识。

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.