The purpose of this NIH F31-Diversity application is to obtain support for the PI, Alana Jones, for
mentored research and career development activities within her MD/PhD degree training that will strengthen her
potential to become an independent physician-scientist. The project goal is to develop skills in genetic
epidemiology and bioinformatics that will allow her to identify genetic and epigenetic risk markers, as well as
develop polygenic and methylation risk scores for chronic kidney disease (CKD) in African Americans (Aims 1
and 2), who experience disproportionately higher incidence and prevalence of disease. Additionally, she will test
the utility of these scores in predicting adverse outcomes associated with CKD, particularly end-stage renal
disease (ESRD) (Aim 3). These methods include genome-wide and epigenome-wide association studies,
multivariate regression modeling, and risk score calibration and discrimination (e.g., C statistic). The primary
objective of this research proposal is to identify individual markers for CKD and consolidate them into a prediction
algorithm. CKD impacts 14% of the US population and is steadily rising as a major cause of mortality globally.
As CKD is asymptomatic in ~90% of people until advanced stages, early risk stratification may be critical to
preventing clinical sequelae, such as ESRD. The central hypothesis is that polygenic and methylation scores
may be able to predict biological CKD risk and its associated outcomes, as both genetic and epigenetic variants
contribute to the heritability of CKD. The long-term objective of her research is to understand how heritable
factors influence health disparities and to develop clinical tools that guide treatment strategies.
The proposed training plan for the PI is sponsored by her project mentor, Dr. Marguerite (Ryan) Irvin.
Included in the training plan are experiences to help the PI develop in the following major areas: 1) rigorous
research in the CKD field, including developing familiarity with the existing literature on CKD epidemiology and
disparities, principles of scientific integrity and responsible conduct of research, and the application of genetic
risk prediction for CKD outcomes; 2) genetic epidemiology, including methodology, interpretation of results, and
critical evaluation of published polygenic and methylation risk scores; and 3) career and professional
development, including learning skills in manuscript and grant writing, journal review, data presentation, and
translation of research findings to clinical application. The overall goal of the training plan is to provide the PI
with a solid foundation for a career as an independent physician-scientist, with the ultimate goal of leading a
collaborative research team that bridges the gap between research on determinants of health disparities and the
implementation of health policy in order to improve cardiovascular health outcomes.