Methylome-wide association study of socioeconomic status, incident type 2 diabetes, and cardiovascular disease events among African Americans

非裔美国人社会经济状况、2 型糖尿病事件和心血管疾病事件的全甲基组关联研究

• 批准号: 10514526
• 负责人: LaShaunta Marie Glover
• 金额: $ 1.37万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-18 至 2022-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10514526
• 关键词: Address; Adult; Affect; African American population; Area; Atherosclerosis Risk in Communities; Award; Biological; Biosocial; Cardiovascular Diseases; Cause of Death; Childhood; DNA Methylation; Data; Dedications; Development; Discipline; Education; Employment; Employment Status; Environment; Epidemiology; Epigenetic Process; Equation; European; Event; Fellowship; Foundations; Future; Gene Expression; Genes; Genetic; Health; Income; Individual; Jackson Heart Study; Lead; Life Experience; Link; Mediating; Mediation; Mediator of activation protein; Mentors; Mentorship; Methods; Methylation; Modeling; Molecular; Movement; National Research Service Awards; Non-Insulin-Dependent Diabetes Mellitus; North Carolina; Occupations; Outcome; Participant; Pathogenesis; Pathologic; Pathway interactions; Phenotype; Population; Population Study; Populations at Risk; Postdoctoral Fellow; Race; Reporting; Research; Research Design; Research Personnel; Research Training; Resources; Risk; Risk Factors; Role; Sampling; Services; Site; Skin; Socioeconomic Status; Students; Suggestion; Therapeutic; Therapeutic Agents; Training; Translating; United States; United States National Institutes of Health; Universities; Women' s Health; cardiometabolism; cardiovascular disorder epidemiology; cardiovascular disorder risk; cardiovascular risk factor; career; design; diabetes risk; disease disparity; epigenetic marker; epigenetic therapy; ethnic diversity; ethnic minority; experience; genetic epidemiology; hazard; insight; low socioeconomic status; methylome; novel; novel marker; pre-doctoral; prevent; skills; social; social epidemiology; social health determinants; socioeconomic adversity; socioeconomic disadvantage; socioeconomics; therapeutic target

Project Abstract This NIH Ruth L. Kirschstein NRSA Individual Predoctoral Fellowship to Promote Diversity in Health-Related Research (F31) application is designed to enhance the training of LáShauntá Glover, MS, a predoctoral student in the Department of Epidemiology at the University of North Carolina at Chapel Hill, and to provide her with the foundation for a career as an independent researcher. Her sponsor, Dr. Kari North and mentors Drs. Laura Loehr, Laura Raffield, and Mario Sims, experts in their respective disciplines, will mentor Ms. Glover. Driven by disparities in type 2 diabetes (T2D) burden, which disproportionately affects African Americans (AAs) and is a strong risk factor for cardiovascular disease (CVD), the proposed research will evaluate the relationship between 2 domains of socioeconomic status (socioeconomic adversity and socioeconomic mobility) and incident T2D, possible epigenetic mechanisms of this effect, and whether these associations relate to downstream CVD. Socioeconomic status (SES) is associated with burden and development of T2D. The consideration of longitudinal outcomes and possible molecular mediators of the SES T2D relationship among AAs could enhance efforts to develop therapeutic agents and prevent the long-term progression of T2D and CVD. Indeed, prior epigenetic research has primarily focused on prevalent T2D, making it difficult to determine whether epigenetic methylation sites are associated with development of T2D, and have not investigated T2D epigenetic pathways to CVD. Studies also use educational attainment as a sole representation of SES, and have not considered cumulative effects of low SES on T2D. Ms. Glover’s proposed research will address these gaps by conducting a study of 2 domains of SES, epigenetic methylation sites, incident T2D and downstream CVD among AA participants of the Jackson Heart Study. In Aim 1, Ms. Glover will characterize the association of cumulative socioeconomic adversity and incident T2D using a score (educational attainment, income, employment, occupation, wealth, and parental education) (n=5306). In Aim 2, Ms. Glover will conduct a methylome-wide association study of 2 domains of SES and incident T2D (n=1757). Finally, in Aim 3, Ms. Glover will evaluate associations by examining the combined effect of 2 domains of SES, epigenetic methylation, and gene expression on incident T2D and downstream CVD using pathway modeling (n=1055). Under the mentorship of her sponsor and mentors who are leaders in the fields of cardiometabolic/cardiovascular epidemiology, genetic/OMICs epidemiology, and social determinants of health, and an environment with numerous training and academic resources, the proposed research and training plan will provide Ms. Glover with the training, skills, and experience to conduct independent research at the intersection of these fields. The proposed research will also yield important insights into the role of upstream socio-epigenetic pathways in T2D risk, providing an essential foundation for future studies seeking to reduce the burden of T2D, and ultimately CVD.

项目摘要 NIH Ruth L. Kirschstein NRSA 个人博士前奖学金旨在促进健康相关领域的多样性 研究 (F31) 申请旨在加强博士前学生 LáShauntá Glover, MS 的培训 在北卡罗来纳大学教堂山分校流行病学系，并为她提供 为独立研究员的职业生涯奠定基础。她的赞助商卡里·诺斯博士和导师。劳拉 洛尔、劳拉·拉菲尔德和马里奥·西姆斯是各自学科的专家，他们将指导格洛弗女士。驱动力 2 型糖尿病 (T2D) 负担的差异，对非裔美国人 (AA) 的影响尤为严重，并且是一个 心血管疾病（CVD）的强烈危险因素，拟议的研究将评估两者之间的关系 2个社会经济地位领域（社会经济逆境和社会经济流动性）和事件T2D， 这种效应可能的表观遗传机制，以及这些关联是否与下游 CVD 相关。 社会经济地位 (SES) 与 T2D 的负担和发展相关。考虑到 AA 之间 SES T2D 关系的纵向结果和可能的分子介质可以增强 努力开发治疗药物并预防 T2D 和 CVD 的长期进展。确实，之前 表观遗传学研究主要集中于流行的 T2D，因此很难确定表观遗传学是否 甲基化位点与 T2D 的发展相关，但尚未研究 T2D 表观遗传途径 到CVD。研究还使用教育程度作为社会经济地位的唯一代表，并且没有考虑 低 SES 对 T2D 的累积影响。格洛弗女士提议的研究将通过进行 AA 中 SES 2 个域、表观遗传甲基化位点、T2D 事件和下游 CVD 的研究 杰克逊心脏研究的参与者。在目标 1 中，Glover 女士将描述累积关联的特征 使用分数（教育程度、收入、就业、 职业、财富和父母教育）（n=5306）。在目标 2 中，Glover 女士将进行全甲基化研究 SES 2 个领域与 T2D 事件的关联研究 (n=1757)。最后，在目标 3 中，Glover 女士将评估 通过检查 SES、表观遗传甲基化和基因的 2 个域的综合效应来确定关联 使用通路模型对事件 T2D 和下游 CVD 的表达进行分析 (n=1055)。在 的指导下 她的赞助商和导师都是心脏代谢/心血管流行病学领域的领导者， 遗传/OMIC 流行病学、健康的社会决定因素以及拥有大量培训和培训的环境 学术资源，拟议的研究和培训计划将为格洛弗女士提供培训、技能和 在这些领域的交叉领域进行独立研究的经验。拟议的研究还将 对上游社会表观遗传途径在 T2D 风险中的作用产生了重要的见解，提供了重要的 为未来寻求减轻 T2D 负担并最终减轻 CVD 负担的研究奠定了基础。