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

项目摘要 这位美国国立卫生研究院的Ruth L. Kirschstein NRSA个人博士前奖学金，以促进健康相关的多样性 研究（F31）应用程序旨在加强LáShauntá格洛弗，MS，博士前学生的培训 在查佩尔山的北卡罗来纳州大学流行病学系，并为她提供 作为独立研究员的职业基础。她的赞助商，博士卡莉北和导师博士劳拉 洛尔、劳拉·拉夫菲尔德和马里奥·西姆斯是各自领域的专家，他们将指导格洛弗女士。驱动 2型糖尿病（T2 D）负担的差异，这不成比例地影响非洲裔美国人（AAs），是一个 心血管疾病（CVD）的强危险因素，拟议的研究将评估 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T2 D事件， 这种影响的可能表观遗传机制，以及这些关联是否与下游CVD有关。 社会经济地位（SES）与T2 D的负担和发展相关。审议 AA之间SES T2 D关系的纵向结果和可能的分子介质可以增强 努力开发治疗剂并预防T2 D和CVD的长期进展。事实上，Prior 表观遗传学研究主要集中在流行的T2 D，使得难以确定表观遗传学是否 甲基化位点与T2 D的发生相关，尚未研究T2 D表观遗传途径 CVD。研究还将教育程度作为社会经济地位的唯一代表， 低SES对T2 D的累积效应。格洛弗女士提出的研究将通过开展 一项关于SES的2个结构域、表观遗传甲基化位点、AA中的偶发T2 D和下游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 社会经济逆境和事件T2 D使用得分（教育程度，收入，就业， 职业、财富和父母教育）（n=5306）。在目标2中，格洛弗女士将进行全甲基化 SES的2个领域与T2 D事件的关联研究（n=1757）。最后，在目标3中，格洛弗女士将评估 通过检查SES的2个结构域，表观遗传甲基化和基因 使用通路建模（n=1055），对事件T2 D和下游CVD的表达进行分析。的辅导下 她的赞助商和导师是心脏代谢/心血管流行病学领域的领导者， 遗传/OMIC流行病学和健康的社会决定因素，以及一个有许多培训和 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， 在这些领域的交叉点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T2 D风险中的作用产生重要的见解，提供了一个重要的 为未来寻求减少T2 D负担的研究奠定基础，最终是CVD。

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.