A survey of the genetics of stomach, liver, and adipose gene expression from a morbidly obese cohort

  1. Lee M. Kaplan4,5,9
  1. 1Merck Research Laboratories, Boston, Massachusetts 02115, USA;
  2. 2Merck Research Laboratories, Rahway, New Jersey 07065, USA;
  3. 3Genetics, Rosetta Inpharmatics LLC, a wholly owned subsidiary of Merck & Co., Inc., Seattle, Washington 98109, USA;
  4. 4Massachusetts General Hospital, Boston, Massachusetts 02114, USA
    1. 5 These authors contributed equally to this work.

    • 6 Present addresses: Johnson & Johnson, Radnor, PA 19087, USA;

    • 7 Sage Bionetworks, Seattle, WA 98109, USA;

    • 8 Pacific Biosciences, Menlo Park, CA 94025, USA.

    Abstract

    To map the genetics of gene expression in metabolically relevant tissues and investigate the diversity of expression SNPs (eSNPs) in multiple tissues from the same individual, we collected four tissues from approximately 1000 patients undergoing Roux-en-Y gastric bypass (RYGB) and clinical traits associated with their weight loss and co-morbidities. We then performed high-throughput genotyping and gene expression profiling and carried out a genome-wide association analyses for more than 100,000 gene expression traits representing four metabolically relevant tissues: liver, omental adipose, subcutaneous adipose, and stomach. We successfully identified 24,531 eSNPs corresponding to about 10,000 distinct genes. This represents the greatest number of eSNPs identified to our knowledge by any study to date and the first study to identify eSNPs from stomach tissue. We then demonstrate how these eSNPs provide a high-quality disease map for each tissue in morbidly obese patients to not only inform genetic associations identified in this cohort, but in previously published genome-wide association studies as well. These data can aid in elucidating the key networks associated with morbid obesity, response to RYGB, and disease as a whole.

    Footnotes

    • 9 Corresponding authors.

      E-mail danielle_greenawalt{at}merck.com.

      E-mail RDobrin{at}ITS.JNJ.COM.

      E-mail eric.schadt{at}gmail.com.

      E-mail lmkaplan{at}partners.org.

    • [Supplemental material is available for this article. The expression data from this study have been submitted to the NCBI Gene Expression Omnibus (GEO; http://www.ncbi.nlm.nih.gov/geo) under super series accession no. GSE24335. Genotyping data will be made available at dbGaP (http://www.ncbi.nlm.nih.gov/gap) and from the Massachusetts General Hospital at http://www.samscore.org.]

    • Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.112821.110.

    • Received July 13, 2010.
    • Accepted April 4, 2011.
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