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

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)应用程序旨在加强对博士生L·肖塔塔·格洛弗的培训 在北卡罗来纳大学教堂山分校流行病学系工作，并为她提供 为独立研究人员的职业生涯奠定了基础。她的赞助人卡里·诺斯博士和她的导师劳拉博士 勒尔、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。驱动者 2型糖尿病(T2D)负担的差异，这对非裔美国人(AA)的影响不成比例，是一种 心血管疾病(CVD)的强烈危险因素，这项拟议的研究将评估 社会经济地位的两个领域(社会经济逆境和社会经济流动性)和事件T2D， 这种影响的可能表观遗传机制，以及这些关联是否与下游心血管疾病有关。 社会经济地位(SES)与T2D的负担和发展有关。考虑到 AAS之间SES T2D关系的纵向结果和可能的分子介质可能增强 努力开发治疗药物，防止T2D和CVD的长期进展。的确，普赖斯 表观遗传学研究主要集中在流行的T2D上，因此很难确定表观遗传学是否 甲基化位点与T2D的发生有关，但尚未研究T2D的表观遗传途径 为心血管疾病干杯。研究还将教育程度作为SES的唯一代表，并未考虑 低SES对T2D的累积效应。格洛弗女士提议的研究将通过以下方式解决这些差距 再生障碍性贫血患者SES两个结构域、表观遗传甲基化位点、T2D事件及下游CVD的研究 杰克逊心脏研究的参与者。在目标1中，格洛弗女士将描述累积与 社会经济逆境和事件T2D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，格洛弗女士将在整个甲基组范围内进行 SES的2个结构域与关联T2D的相关性研究(n=1757)。最后，在《目标3》中，格洛弗女士将评估 通过检查SES的两个结构域、表观遗传甲基化和基因的联合效应来研究它们之间的关联 使用通路模型(n=1055)在入射T2D和下游CVD上的表达。在…的指导下 她的赞助人和导师是心脏代谢/心血管流行病学领域的领导者， 遗传/组学流行病学，健康的社会决定因素，以及经过大量培训和 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风险中的作用提供了重要的见解，提供了必要的 为未来寻求减轻T2D和最终心血管疾病负担的研究奠定基础。

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.