Sociocultural factors, DNA methylation and Risk of Diabetes in Hispanics/Latinos

西班牙裔/拉丁裔是美国最大和增长最快的少数民族群体， 2型糖尿病（T2 D）。社会文化、社会心理和行为因素[统称为 “社会环境因素”被认为是西班牙裔/拉丁裔T2 D差异的原因，但 它们进入皮肤下的机制尚不清楚。DNA甲基化（DNAm）是最常见的 研究表观遗传修饰，是响应各种社会环境暴露在一个人的 生命过程中，和异常DNAm已与衰老和年龄相关的疾病，包括T2 D。到 迄今为止，人们对与社会环境暴露相关的全基因组DNA模式知之甚少。 总体称为“社会环境问题”]。社会环境的机制 肿瘤在生物学上嵌入到衰老中，T2 D的风险尚未在一项研究中得到很好的研究。 西班牙裔/拉丁裔的全国代表性样本。基于我们之前的工作，我们假设 社会环境风险和保护因素诱发的DNA m有助于T2 D的风险， 西班牙裔/拉丁裔。我们的目标是描述与风险有关的社会环境问题 的T2 D，并确定关键的生物途径，通过社会环境问题影响的风险， 糖尿病，独立于已知的风险因素。为了实现这一目标，我们利用大量的深度临床表型 西班牙裔社区健康研究/拉丁裔研究收集的社会环境因素 (HCHS/SOL）及其辅助研究-社会文化辅助研究。利用外周血基因组 在基线（2008-2011年）从3，323名非糖尿病西班牙裔/拉丁裔（18-74岁）中收集DNA， 到2024年，我们将首先使用统一的理论框架确定独特的潜在结构，然后 进行表观基因组关联研究（EWAS），以识别甲基化基因/区域， 独特的社会环境结构（目标1）。西班牙裔/拉丁裔的调查结果将在非西班牙裔/拉丁裔中复制。 西班牙裔白人、非裔美国人和美洲印第安人（总计N= 7，184）。在目标2中，我们预期 确定社会环境诱导的DNAm是否可以预测T2 D的发作和进展， 标准临床因素。在目标3中，我们将进行综合遗传和表观遗传分析，以确定因果关系， 表观遗传介质和分子途径，通过这些介质和分子途径， 西班牙裔/拉丁裔的糖尿病风险。该项目的成功完成将确定 可改变的基因和因果途径，通过这些途径，社会环境因素在生物学上 西班牙裔的心脏代谢健康这些结果可能提供新的机制见解， 疾病病理学，并可能导致糖尿病预防的文化定制的精确策略， 因此，我们需要采取干预措施，从而减少这一少数群体中的糖尿病差异。

Hispanics/Latinos, the largest and fastest-growing minority group in the US, are disproportionately affected by type 2 diabetes (T2D). Sociocultural, psychosocial, and behavioral factors [collectively called “socioenvironmental factors” hereafter] are believed to contribute to T2D disparity in Hispanics/Latinos, but the mechanisms through which they get under the skin are unclear. DNA methylation (DNAm), one of the most studied epigenetic modifications, is responsive to various socioenvironmental exposures across an individual’s life course, and aberrant DNAm has been associated with aging and age-related diseases including T2D. To date, little is known about the genomewide DNAm patterns associated with socioenvironmental exposures [in totality named “socioenvironmental exposome”]. The mechanisms through which socioenvironmental exposome becomes biologically embedded into aging and risk of T2D have not been well studied in a nationally representative sample of Hispanics/Latinos. Building on our prior work, we hypothesize that altered DNAm evoked by socioenvironmental risk and protective factors contributes to risk for T2D in Hispanics/Latinos. Our objectives here are to characterize the socioenvironmental exposome in relation to risk of T2D, and identify key biological pathways through which socioenvironmental exposome affects risk of diabetes, independent of known risk factors. To achieve this, we leverage a wealth of deep clinical phenotypes and socioenvironmental factors collected by the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and its ancillary study - the Sociocultural Ancillary Study (SCAS). Using peripheral blood genomic DNA collected at baseline (2008-2011) from 3,323 non-diabetic Hispanics/Latinos (aged 18-74) followed through 2024, we will first identify unique latent constructs using a unified theoretical framework and then conduct epigenomewide association studies (EWAS) to identify methylated genes/regions in response to each unique socioenvironmental construct (Aim 1). Findings from Hispanics/Latinos will be replicated in non- Hispanic Whites, African Americans, and American Indians (total N=7,184). In Aim 2, we will prospectively determine whether socioenvironment-induced DNAm predict the onset and progression of T2D, independent of standard clinical factors. In Aim 3, we will perform integrated genetic and epigenetic analyses to identify causal epigenetic mediators and molecular pathways through which socioenvironmental exposome become biologically embedded into diabetes risk in Hispanics/Latinos. Successful completion of this project will identify modifiable genes and causal pathways through which socioenvironmental factors become biologically embedded in Hispanic cardiometabolic health. Such results may provide novel mechanistic insights into disease pathology, and are likely to lead to culturally tailored precision strategies for diabetes prevention and intervention, thereby reducing diabetes disparity in this minority population.