Abstract 20688: A Phenome-Wide Association Study to Assess Pleiotropic Effects of LPA

Introduction: Lipoprotein(a) (Lp(a)) is a risk factor for atherosclerosis but its physiological function remains obscure. Furthermore, the potential introduction of LPA targeting therapies into clinical practice warrants an assessment of non-lipid effects of LPA. Objective: We conducted an electronic health record (EHR)-based phenome-wide association study (PheWAS) in the electronic MEdical Records and GEnomics (eMERGE) Network to determine associations of LPA variants and a range of human phenotypes. Methods: High-density genotype data linked to the EHR were available in 60,995 non-Hispanic whites (mean age 60±24 years, 52% females). A set of cases and controls was defined for each phenotype using the PheWAS R package; 13,707 diagnosis codes were converted to 1,814 phenocodes. We tested 10 LPA variants (associated with plasma Lp(a) levels, minor allele frequency (MAF) ≥0.1%, INFO score >0.7, CADD score >1) with 895 EHR-derived binary phenotypes (≥300 cases per trait) using logistic regression assuming an...