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

西班牙裔/拉丁裔的社会文化因素、DNA 甲基化和糖尿病风险

• 批准号: 10735009
• 负责人: Jinying Zhao
• 金额: $ 68.22万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-09-15 至 2026-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10735009
• 关键词: Aberrant DNA Methylation; Acceleration; Affect; African American population; Aging; American Indians; Ancillary Study; Behavior; Behavioral; Biological; Blood; Body mass index; Central American; Clinical; Clinical Data; Communities; Cuban; DNA; DNA Methylation; Data; Diabetes Mellitus; Diabetes prevention; Disease; Disparity; Dominican; Epidemiology; Epigenetic Process; Equation; Ethnic Origin; Ethnic Population; Factor Analysis; Genes; Genetic; Genomic DNA; Health; Hispanic; Hispanic Community Health Study/Study of Latinos; Hispanic Populations; Individual; Insulin Resistance; Intervention; Latino; Latino Population; Life Cycle Stages; Life Style; Longitudinal cohort; Maps; Mediator; Meta-Analysis; Methylation; Mexican; Minority Groups; Modeling; Modification; Molecular; Multivariate Analysis; Names; Non-Insulin-Dependent Diabetes Mellitus; Not Hispanic or Latino; Participant; Pathology; Pathway interactions; Pattern; Persons; Population Heterogeneity; Psychosocial Factor; Puerto Rican; Random Allocation; Risk; Risk Factors; Sampling; Skin; Social Environment; South American; Subgroup; Survival Analysis; Validation; Woman; Work; age related; aged; bead chip; bisulfite; cardiometabolism; clinical phenotype; cohort; design; diabetes risk; fasting glucose; follow-up; genome wide association study; genome-wide; high risk; individualized prevention; insight; lifestyle factors; lifetime risk; men; methylation pattern; methylome; non-diabetic; novel; peripheral blood; personalized intervention; prognostic; prospective; protective factors; psychosocial; pyrosequencing; resilience; resilience factor; response; social culture; sociocultural determinant; socioenvironmental factor

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.

西班牙裔/拉丁裔是美国最大，最快的少数群体，受到了不成比例的影响 2型糖尿病（T2D）。社会文化，社会心理和行为因素[共同称为 据信，“社会环境因素”]被认为有助于西班牙裔/拉丁美洲人的T2D差异，但是 它们在皮肤下的机制尚不清楚。 DNA甲基化（DNAM），其中一种 研究菌的表观遗传修饰，对个人的各种社会环境暴露有反应 生命过程和异常DNA与包括T2D在内的衰老和与年龄有关的疾病有关。到 日期，关于与社会环境暴露相关的全基因组dnam模式知之甚少[ 总体称为“社会环境杂物”]。社会环境的机制 外向体在生物学上嵌入到衰老中，而T2D的风险在A中并没有很好地研究 全国代表性的西班牙裔/拉丁裔样本。在我们先前的工作的基础上，我们假设发生了变化 dnam受到社会环境风险和保护因素的影响，导致T2D风险 西班牙裔/拉丁裔。我们这里的目的是描述与风险有关 T2D，并确定社会环境暴露的关键生物学途径 糖尿病，独立于已知危险因素。为了实现这一目标，我们利用大量深层临床表型 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（SCAS）。使用外周血基因组 从3,323个非糖尿病西班牙裔/拉丁美洲人（18-74岁）在基线（2008-2011）收集的DNA随后 到2024年，我们将首先使用统一的理论框架确定独特的潜在构建体，然后 进行表观性的整个关联研究（EWAS），以鉴定每种甲基化基因/区域 独特的社会环境结构（AIM 1）。来自西班牙裔/拉丁美洲人的发现将在非 - 西班牙裔白人，非裔美国人和美国印第安人（总数n = 7,184）。在AIM 2中，我们可能会 确定社会环境引起的DNAM是否预测T2D的发作和进展，独立于 标准临床因素。在AIM 3中，我们将执行综合的遗传和表观遗传分析以识别催化 表观遗传介质和分子途径通过，社会环境杂志成为 在西班牙裔/拉丁裔中，生物学嵌入糖尿病风险中。成功完成该项目将确定 可修改的基因和因果途径，社会环境因素从生物学上开始 嵌入西班牙裔心脏代谢健康中。这样的结果可能会为您提供新的机械见解 疾病病理学，很可能导致针对预防糖尿病的文化量身定制的精确策略 干预措施，从而减少了这一少数人群的糖尿病差异。