title: Evidence for extensive pleiotropy among pharmacogenes.
abstract: We sought to identify potential pleiotropy involving pharmacogenes.
  
  
  
  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.
  
  
  
  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).
  
  
  
  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).
authors.affiliation: Center for Human Genetics Research, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Matthew T
authors.initials: MT
authors.lastname: Oetjens
authors.affiliation: Department of Epidemiology & Biostatistics, Institute for Computational Biology, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: William S
authors.initials: WS
authors.lastname: Bush
authors.affiliation: Department of Biomedical Informatics, Vanderbilt University, Nashville, TN 37203, USA.
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Denny
authors.affiliation: Department of Medicine, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Kelly
authors.initials: K
authors.lastname: Birdwell
authors.affiliation: Center for Human Genetics Research, Vanderbilt University, Nashville, TN 37232, USA.
authors.forename: Nuri
authors.initials: N
authors.lastname: Kodaman
authors.affiliation: Center for Systems Genomics, Department of Biochemistry & Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Anurag
authors.initials: A
authors.lastname: Verma
authors.affiliation: Sarah Cannon Research Institute, Nashville, TN 37203 USA.
authors.forename: Holli H
authors.initials: HH
authors.lastname: Dilks
authors.affiliation: Center for Systems Genomics, Department of Biochemistry & Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Pendergrass
authors.affiliation: Center for Systems Genomics, Department of Biochemistry & Molecular Biology, The Pennsylvania State University, University Park, PA 16802, USA.
authors.forename: Marylyn D
authors.initials: MD
authors.lastname: Ritchie
authors.affiliation: Department of Epidemiology & Biostatistics, Institute for Computational Biology, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: Dana C
authors.initials: DC
authors.lastname: Crawford
mesh_terms: D000328:Adult; D001741:Black or African American; D065731:Cytochrome P-450 CYP2C19 / Q000235:genetics; D005260:Female; D058685:Genetic Pleiotropy; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D010597:Pharmacogenetics; D010641:Phenotype; D027981:Symporters / Q000235:genetics
chemical_list: D027981:Symporters; C093694:hydrogen-coupled oligopeptide transporter PepT2; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19
keywords: absorption, distribution, metabolism and excretion; electronic health records; genetic association study; pharmacogenomics; phenome-wide association study