A Phenome-Wide Association Study to Identify and Characterize Phenotypic Effects of Lp(a)

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Project Summary/Abstract This NIH Kirschstein-NRSA postdoctoral fellowship (F32) application is designed to promote the training of Dr. Moa Lee, PharmD, MPH, a post-doctoral fellow and concurrent Epidemiology PhD student at the University of North Carolina, and to provide her with the foundation for an independent research career. Building upon her clinical training and research experience in the fields of pharmacy and pharmacoepidemiology, Dr. Lee's goal is to expand her research horizon into pharmacogenomics research under the sponsorship of two highly successful genetic epidemiologists. This advanced training will enable Dr. Lee to further contribute to advancing the clinical knowledge and research base underlying optimal treatment decisions. The proposed research project is deliberately designed to leverage Dr. Lee's research experience using dense phenotypic data while providing extensive training to acquire the remaining competencies in genetic epidemiology and career development. Driven by the need to improve current prevention and treatment strategies for cardiovascular disease (CVD), Dr. Lee will interrogate lipoprotein (a) [Lp(a)]. Emerging evidence has identified Lp(a), a highly atherogenic, low density lipoprotein-like moiety, as an attractive novel therapeutic target. Given that the current understanding of the role of Lp(a) in CVD is limited, particularly with respect to emerging evidence that Lp(a) may affect a broader range of phenotypes, the proposed research will comprehensively interrogate the effects of Lp(a) on health and disease. Specifically, Dr. Lee proposes a phenome-wide association study (PheWAS) of Lp(a), a novel approach to assess the effects of Lp(a) across a broad range of phenotype domains. By helping ensure temporality in exposure effects and limiting bias from confounding, a Lp(a) PheWAS is uniquely positioned to provide new insights into the underlying pathogenesis of Lp(a), uncover novel associations, and, ultimately, inform understanding unanticipated side effects of potential treatments. Dr. Lee's deliberate selection of a large (n~600,000), deeply phenotyped, multi-ethnic population spanning early to late adulthood with a large proportion of females will increase the generalizability of study findings. Together, this proposal will provide Dr. Lee with a solid foundation in genetic epidemiology. The knowledge and experience as well as the preliminary data afforded by this proposal will provide the groundwork for Dr. Lee's future research agenda as well as investigator-initiated applications as she embarks on an independent and interdisciplinary research career.