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

doi:10.2217/pgs-2015-0007

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 journal › Article › peer-review

11 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 language	English (US)
Pages (from-to)	853-866
Number of pages	14
Journal	Pharmacogenomics
Volume	17
Issue number	8
DOIs	https://doi.org/10.2217/pgs-2015-0007
State	Published - Jun 2016

All Science Journal Classification (ASJC) codes

Molecular Medicine
Genetics
Pharmacology

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title = "Evidence for extensive pleiotropy among pharmacogenes",

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).",

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

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year = "2016",

month = jun,

doi = "10.2217/pgs-2015-0007",

language = "English (US)",

volume = "17",

pages = "853--866",

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T1 - Evidence for extensive pleiotropy among pharmacogenes

AU - Oetjens, Matthew T.

AU - Bush, William S.

AU - Denny, Joshua C.

AU - Birdwell, Kelly

AU - Kodaman, Nuri

AU - Verma, Anurag

AU - DIlks, Holli H.

AU - Pendergrass, Sarah A.

AU - Ritchie, Marylyn D.

AU - Crawford, Dana C.

PY - 2016/6

Y1 - 2016/6

N2 - 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).

AB - 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).

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Evidence for extensive pleiotropy among pharmacogenes

Abstract

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