We conducted an electronic health record (EHR)-based phenome-wide association study (PheWAS) to discover pleiotropic effects of variants in three lipoprotein metabolism genes , , and . Using high-density genotype data, we tested the associations of variants in the three genes with 1232 EHR-derived binary phecodes in 51,700 European-ancestry (EA) individuals and 585 phecodes in 10,276 African-ancestry (AA) individuals; 457 , 730 , and 720 variants were filtered by imputation quality ( > 0.4), minor allele frequency (>1%), linkage disequilibrium ( < 0.3), and association with LDL-C levels, yielding a set of two , three , and five variants in EA but no variants in AA. Cases and controls were defined for each phecode using the PheWAS package in R. Logistic regression assuming an additive genetic model was used with adjustment for age, sex, and the first two principal components. Significant associations were tested in additional cohorts from Vanderbilt University ( = 29,713), the Marshfield Clinic Personalized Medicine Research Project ( = 9562), and UK Biobank ( = 408,455). We identified one , two , and two variants significantly associated with an examined phecode. Only one of the variants was associated with a non-lipid disease phecode, ("myopia") but this association was not significant in the replication cohorts. In this large-scale PheWAS we did not find LDL-C-related variants in , , and to be associated with non-lipid-related phenotypes including diabetes, neurocognitive disorders, or cataracts.