title: Transcriptomic variation of pharmacogenes in multiple human tissues and lymphoblastoid cell lines.
abstract: Variation in the expression level and activity of genes involved in drug disposition and action ('pharmacogenes') can affect drug response and toxicity, especially when in tissues of pharmacological importance. Previous studies have relied primarily on microarrays to understand gene expression differences, or have focused on a single tissue or small number of samples. The goal of this study was to use RNA-sequencing (RNA-seq) to determine the expression levels and alternative splicing of 389 Pharmacogenomics Research Network pharmacogenes across four tissues (liver, kidney, heart and adipose) and lymphoblastoid cell lines, which are used widely in pharmacogenomics studies. Analysis of RNA-seq data from 139 different individuals across the 5 tissues (20-45 individuals per tissue type) revealed substantial variation in both expression levels and splicing across samples and tissue types. Comparison with GTEx data yielded a consistent picture. This in-depth exploration also revealed 183 splicing events in pharmacogenes that were previously not annotated. Overall, this study serves as a rich resource for the research community to inform biomarker and drug discovery and use.
authors: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
authors: A
authors: A
authors: Chhibber
authors: Departments of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
authors: C E
authors: CE
authors: French
authors: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
authors: S W
authors: SW
authors: Yee
authors: Division of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, TN, USA.|Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors: E R
authors: ER
authors: Gamazon
authors: Children's Hospital Oakland Research Institute, Oakland, CA, USA.
authors: E
authors: E
authors: Theusch
authors: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
authors: X
authors: X
authors: Qin
authors: Department of Biomedical Informatics, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors: A
authors: A
authors: Webb
authors: Center for Pharmacogenomics; College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.
authors: A C
authors: AC
authors: Papp
authors: Children's Hospital Oakland Research Institute, Oakland, CA, USA.
authors: A
authors: A
authors: Wang
authors: Division of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, TN, USA.
authors: C Q
authors: CQ
authors: Simmons
authors: Division of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, TN, USA.
authors: A
authors: A
authors: Konkashbaev
authors: Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors: A S
authors: AS
authors: Chaudhry
authors: Children's Hospital Oakland Research Institute, Oakland, CA, USA.
authors: K
authors: K
authors: Mitchel
authors: Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
authors: D
authors: D
authors: Stryke
authors: Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA.
authors: T E
authors: TE
authors: Ferrin
authors: Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
authors: S T
authors: ST
authors: Weiss
authors: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
authors: D L
authors: DL
authors: Kroetz
authors: Center for Pharmacogenomics; College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA.|Departments of Pharmacology, Psychiatry, and Human Genetics/Internal Medicine, College of Medicine; Colleges of Pharmacy and Environmental Health Sciences, The Ohio State University, Columbus, OH, USA.
authors: W
authors: W
authors: Sadee
authors: Department of Genome Sciences, University of Washington, Seattle, WA, USA.
authors: D A
authors: DA
authors: Nickerson
authors: Children's Hospital Oakland Research Institute, Oakland, CA, USA.
authors: R M
authors: RM
authors: Krauss
authors: Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
authors: A L
authors: AL
authors: George
authors: Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA.
authors: E G
authors: EG
authors: Schuetz
authors: Children's Hospital Oakland Research Institute, Oakland, CA, USA.
authors: M W
authors: MW
authors: Medina
authors: Division of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, TN, USA.
authors: N J
authors: NJ
authors: Cox
authors: Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA.
authors: S E
authors: SE
authors: Scherer
authors: Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA.
authors: K M
authors: KM
authors: Giacomini
authors: Departments of Molecular and Cell Biology, University of California, Berkeley, CA, USA.|Department of Plant and Microbial Biology, University of California, Berkeley, CA, USA.
authors: S E
authors: SE
authors: Brenner
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D017398:Alternative Splicing; D002460:Cell Line; D019295:Computational Biology; D030541:Databases, Genetic; D005838:Genotype; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D010597:Pharmacogenetics; D000071184:Pharmacogenomic Variants; D010641:Phenotype; D017423:Sequence Analysis, RNA; D059467:Transcriptome