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

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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.