Integrating disease and drug-related phenotypes for improved identification of pharmacogenomic variants.

To improve the identification and interpretation of pharmacogenetic variants through the integration of disease and drug-related traits. We hypothesized that integrating genome-wide disease and pharmacogenomic data may drive new insights into drug toxicity and response by identifying shared genetic architecture. Pleiotropic variants were identified using a methodological framework incorporating colocalization analysis. Using genome-wide association studies summary statistics from the UK Biobank, European Bioinformatics Institute genome-wide association studies catalog and the Pharmacogenomics Research Network, we validated pleiotropy at the locus between allopurinol response and gout and identified novel pleiotropy between antihypertensive-induced new-onset diabetes, Crohn's disease and inflammatory bowel disease at the locus. New mechanistic insights and genetic loci can be uncovered by identifying pleiotropy between disease and drug-related traits.