Abstract
Aim: To improve the identification and interpretation of pharmacogenetic variants through the integration of disease and drug-related traits. Materials & methods: 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. Results: 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 ABCG2 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 IL18RAP/SLC9A4 locus. Conclusion: New mechanistic insights and genetic loci can be uncovered by identifying pleiotropy between disease and drug-related traits.
Citation
Ouellette, Tom W, Wright, Galen Eb, Drögemöller, Britt I. Ross, Colin Jd, Carleton, Bruce C, “Integrating Disease and Drug-Related Phenotypes for Improved Identification of Pharmacogenomic Variants,” Pharmacogenomics 22, 5(2021): 251-261, doi: 10.2217/pgs-2020-0130