Evidence for extensive pleiotropy among pharmacogenes. (June 2016)

• Record Type: Journal Article
• Authors: Oetjens, Matthew T; Bush, William S; Denny, Joshua C; Birdwell, Kelly; Kodaman, Nuri; Verma, Anurag; Dilks, Holli H; Pendergrass, Sarah A; Ritchie, Marylyn D; Crawford, Dana C
• Is Part Of: Pharmacogenomics. Volume 17:Number 8(2016)
• Page Start: 853
• Page End: 866
• Publication Date: 2016-06
• Subjects: absorption, distribution, metabolism and excretion -- electronic health records -- genetic association study -- pharmacogenomics -- phenome-wide association study; Pharmacogenomics -- Periodicals; 615.1
• DOI: 10.2217/pgs-2015-0007
• Languages: English
• ISSNs: 1462-2416

Abstract

Aim: We sought to identify potential pleiotropy involving pharmacogenes.Methods: We tested 184 functional variants in 34 pharmacogenes for associations using a custom grouping of International Classification and Disease, Ninth Revision billing codes extracted from deidentified electronic health records of 6892 patients.Results: We replicated several associations including ABCG2 (rs2231142) and gout (p = 1.73 × 10 -7 ; odds ratio [OR]: 1.73; 95% CI: 1.40–2.12); and SLCO1B1 (rs4149056) and jaundice (p = 2.50 × 10 -4 ; OR: 1.67; 95% CI: 1.27–2.20).Conclusion: In this systematic screen for phenotypic associations with functional variants, several novel genotype–phenotype combinations also achieved phenome-wide significance, including SLC15A2 rs1143672 and renal osteodystrophy (p = 2.67 × 10 - 6 ; OR: 0.61; 95% CI: 0.49–0.75).