Evidence for extensive pleiotropy among pharmacogenes-Reference-Cited by-同舟云学术

Evidence for extensive pleiotropy among pharmacogenes

Published:2016-06 Issue:8 Volume:17 Page:853-866
ISSN:1462-2416
Container-title:Pharmacogenomics
language:en
Short-container-title:Pharmacogenomics

Author:

Oetjens Matthew T¹,Bush William S²,Denny Joshua C³,Birdwell Kelly⁴,Kodaman Nuri¹,Verma Anurag⁵,Dilks Holli H⁶,Pendergrass Sarah A⁵,Ritchie Marylyn D⁵,Crawford Dana C²

Affiliation:

1. Center for Human Genetics Research, Vanderbilt University, Nashville, TN 37232, USA

2. Department of Epidemiology & Biostatistics, Institute for Computational Biology, Case Western Reserve University, Cleveland, OH 44106, USA

3. Department of Biomedical Informatics, Vanderbilt University, Nashville, TN 37203, USA

4. Department of Medicine, Vanderbilt University, Nashville, TN 37232, USA

5. Center for Systems Genomics, Department of Biochemistry & Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA

6. Sarah Cannon Research Institute, Nashville, TN 37203 USA

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).

Publisher

Future Medicine Ltd

Subject

Pharmacology,Genetics,Molecular Medicine

Link

https://www.futuremedicine.com/doi/pdf/10.2217/pgs-2015-0007

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