Matthew T Oetjens1, William S Bush2, Joshua C Denny3, Kelly Birdwell4, Nuri Kodaman1, Anurag Verma5, Holli H Dilks6, Sarah A Pendergrass5, Marylyn D Ritchie5, Dana C Crawford2. 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).
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 SLC15A2rs1143672 and renal osteodystrophy (p = 2.67 × 10(-) (6); OR: 0.61; 95% CI: 0.49-0.75).
Entities:
Keywords:
absorption, distribution, metabolism and excretion; electronic health records; genetic association study; pharmacogenomics; phenome-wide association study
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