Original Article

The Pharmacogenomics Journal (2017) 17, 137–145; doi:10.1038/tpj.2015.93; published online 9 February 2016

Transcriptomic variation of pharmacogenes in multiple human tissues and lymphoblastoid cell lines
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A Chhibber1,16, C E French2,16, S W Yee1,16, E R Gamazon3,4,16, E Theusch5, X Qin6, A Webb7, A C Papp8, A Wang5, C Q Simmons3, A Konkashbaev3, A S Chaudhry9, K Mitchel5, D Stryke10, T E Ferrin10, S T Weiss11, D L Kroetz1, W Sadee8,12, D A Nickerson13, R M Krauss5, A L George14, E G Schuetz9, M W Medina5, N J Cox3, S E Scherer6, K M Giacomini1 and S E Brenner2,15

  1. 1Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, CA, USA
  2. 2Departments of Molecular and Cell Biology, University of California, Berkeley, CA, USA
  3. 3Division of Genetic Medicine, Department of Medicine, Vanderbilt University, Nashville, TN, USA
  4. 4Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
  5. 5Children's Hospital Oakland Research Institute, Oakland, CA, USA
  6. 6Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA
  7. 7Department of Biomedical Informatics, College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA
  8. 8Center for Pharmacogenomics; College of Medicine, The Ohio State University Wexner Medical Center, Columbus, OH, USA
  9. 9Department of Pharmaceutical Sciences, St. Jude Children's Research Hospital, Memphis, TN, USA
  10. 10Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, CA, USA
  11. 11Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA
  12. 12Departments 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
  13. 13Department of Genome Sciences, University of Washington, Seattle, WA, USA
  14. 14Department of Pharmacology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
  15. 15Department of Plant and Microbial Biology, University of California, Berkeley, CA, USA

Correspondence: Dr S Scherer, Human Genome Sequencing Center, Baylor College of Medicine, Houston, TX, USA E-mail: sscherer@bcm.edu; Dr K Giacomini, Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, USA E-mail: kathy.giacomini@ucsf.edu; Dr SE Brenner, Department of Plant and Microbial Biology, University of California, Berkeley, CA 94720-3102, USA. E-mail: brenner@compbio.berkeley.edu

16Co-first authors.

Received 8 May 2015; Revised 6 November 2015; Accepted 13 November 2015
Advance online publication 9 February 2016

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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.