PROJECT SUMMARY The long-term goal of this project is to assess the utility of multi-ancestry polygenic risk scores (PRSs) in large real-world cohorts to predict health outcomes in clinical settings. PRSs represent a numerical summary of an individuals’ genetic risk for a trait or disease based on combined effects of genetic variants across the human genome. A PRS has many potential benefits such as efficient disease screening/prediction and therapeutic prevention/intervention and may be useful in saving many lives and resources. However, the application of PRS for risk prediction in clinical settings alongside non-genetic risk factors such as lifestyle and environmental risk factors remains largely unknown. A better understanding of PRS utility for clinical risk prediction, and limitations of PRS in real-world populations is needed to realize the potential benefits of the applications of PRS for all populations. This proposal encompasses a training and research plan to develop the candidate’s expertise in genetic epidemiology research. The specific aims are to 1a) Investigate the association of multi-ancestry blood pressure (BP) PRS with hypertension incidence and progression in individuals across their life course, 1b) Investigate the association of multi-ancestry BP PRS with incidence of BP-related health outcomes including stroke, cardiovascular disease (CVD), dementia, kidney disease, heart failure and all-cause mortality (F99 dissertation research. This proposed project will generate new knowledge and provide training for the candidate’s advancement to become an independent investigator focused on genetic epidemiology of complex polygenic diseases and traits. The research is relevant to NHGRI’s bold predictions by 2030, number 6 “The regular use of genomic information will have transitioned from boutique to mainstream in all clinical settings, making genomic testing as routine as complete blood counts”.