Using genetic variation to study biology of blood lipids & coronary heart disease

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Abstract Mitral valve prolapse (MVP) is a common yet underrecognized condition carrying significant morbidity and mortality. Current management only includes surveillance and surgery. While genomic character- ization has emerged as a tool to prioritize targets for medicines and improve risk prediction, such analyses for MVP are relatively underpowered compared to many cardiovascular traits due to under recognition. The goal of this administrative supplement is to study the genetics of MVP using a large- scale genome-wide association study of over 18,000 MVP cases. Our research team combines strengths in cardiovascular medicine, statistical genetics, and high-throughput genetics and ge- nomics. In Aim 1, we will develop a natural-language processing-based definition of MVP and MVP sub-phenotypes to improve case identification. We will then complete a genome-wide association study of MVP and MVP sub-phenotypes. In Aim 2, we will develop a polygenic risk score framework to stratify risk of sudden cardiac death among individuals with MVP. This administrative supplement will leverage the infrastructure we have built through the Global Lipids Genetics Consortium (GLGC) and our established collaborative relationships. Completion of our aims will provide new insights that have the potential to catalyze breakthroughs in prevention, treatment, and diagnosis of MVP.