Evidence for extensive pleiotropy among pharmacogenes

Matthew T. Oetjens, William S. Bush, Joshua C. Denny, Kelly Birdwell, Nuri Kodaman, Anurag Verma, Holli H. DIlks, Sarah A. Pendergrass, Marylyn D. Ritchie, Dana C. Crawford

Research output: Contribution to journalArticle

5 Scopus citations

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).

Original languageEnglish (US)
Pages (from-to)853-866
Number of pages14
JournalPharmacogenomics
Volume17
Issue number8
DOIs
StatePublished - Jun 2016

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Genetics
  • Pharmacology

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    Oetjens, M. T., Bush, W. S., Denny, J. C., Birdwell, K., Kodaman, N., Verma, A., DIlks, H. H., Pendergrass, S. A., Ritchie, M. D., & Crawford, D. C. (2016). Evidence for extensive pleiotropy among pharmacogenes. Pharmacogenomics, 17(8), 853-866. https://doi.org/10.2217/pgs-2015-0007