title: A survey of the genetics of stomach, liver, and adipose gene expression from a morbidly obese cohort.
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.
authors: Merck Research Laboratories, Boston, MA 02115, USA. danielle_greenawalt@merck.com
authors: Danielle M
authors: DM
authors: Greenawalt
authors: Radu
authors: R
authors: Dobrin
authors: Eugene
authors: E
authors: Chudin
authors: Ida J
authors: IJ
authors: Hatoum
authors: Christine
authors: C
authors: Suver
authors: John
authors: J
authors: Beaulaurier
authors: Bin
authors: B
authors: Zhang
authors: Victor
authors: V
authors: Castro
authors: Jun
authors: J
authors: Zhu
authors: Solveig K
authors: SK
authors: Sieberts
authors: Susanna
authors: S
authors: Wang
authors: Cliona
authors: C
authors: Molony
authors: Steven B
authors: SB
authors: Heymsfield
authors: Daniel M
authors: DM
authors: Kemp
authors: Marc L
authors: ML
authors: Reitman
authors: Pek Yee
authors: PY
authors: Lum
authors: Eric E
authors: EE
authors: Schadt
authors: Lee M
authors: LM
authors: Kaplan
references: Nature. 2008 Mar 27;452(7186):423-8
references: 18344981
references: Diabetes Metab Rev. 1991 Sep;7(3):139-53
references: 1816999
references: Nat Genet. 2009 May;41(5):591-5
references: 19349983
references: BMC Med Genet. 2007 Sep 19;8 Suppl 1:S16
references: 17903298
references: Proteomics. 2007 Jun;7(13):2216-21
references: 17549794
references: Nat Biotechnol. 2001 Apr;19(4):342-7
references: 11283592
references: Science. 2002 Aug 30;297(5586):1551-5
references: 12202830
references: Bioinformatics. 2008 Mar 1;24(5):719-20
references: 18024473
references: Nat Genet. 2008 Feb;40(2):161-9
references: 18193043
references: Hum Mol Genet. 2009 Sep 15;18(18):3502-7
references: 19553259
references: Physiol Genomics. 2006 Oct 11;27(2):114-21
references: 16849634
references: BMC Med Genomics. 2010 Jan 27;3:3
references: 20105310
references: Genome Res. 2009 Jul;19(7):1316-23
references: 19498102
references: Diabetes. 2008 Aug;57(8):2253-7
references: 18556336
references: Nature. 2008 Mar 27;452(7186):429-35
references: 18344982
references: Nat Genet. 2000 May;25(1):87-90
references: 10802663
references: Obes Surg. 2011 Jul;21(7):930-4
references: 20957447
references: EMBO Rep. 2007 Dec;8(12):1183-9
references: 17932511
references: Am J Med. 2008 Oct;121(10):885-93
references: 18823860
references: Nat Genet. 2009 Jan;41(1):25-34
references: 19079261
references: Nat Genet. 2009 Feb;41(2):157-9
references: 19151714
references: Science. 2007 Jun 1;316(5829):1331-6
references: 17463246
references: Am J Hum Genet. 2007 Aug;81(2):338-45
references: 17668382
references: Nat Clin Pract Endocrinol Metab. 2008 Oct;4(10):569-77
references: 18779842
references: Genome Res. 2010 Aug;20(8):1020-36
references: 20538623
references: J Mol Med (Berl). 2007 Feb;85(2):129-37
references: 17089095
references: Hum Genet. 2009 Oct;126(4):567-74
references: 19526250
references: Nat Genet. 2009 Jan;41(1):35-46
references: 19060910
references: BMC Med Genet. 2009 Jan 22;10:6
references: 19161620
references: Arterioscler Thromb Vasc Biol. 2006 Aug;26(8):1828-36
references: 16763159
references: JAMA. 2004 Oct 13;292(14):1724-37
references: 15479938
references: Stat Appl Genet Mol Biol. 2005;4:Article17
references: 16646834
references: PLoS Genet. 2010 Apr 01;6(4):e1000895
references: 20369022
references: Cell Physiol Biochem. 2008;22(5-6):515-24
references: 19088433
references: Am J Hum Genet. 2007 Sep;81(3):559-75
references: 17701901
references: Nat Genet. 2009 Jan;41(1):47-55
references: 19060911
references: Am J Med Genet B Neuropsychiatr Genet. 2004 Apr 1;126B(1):124-7
references: 15048662
references: Nat Genet. 2006 Aug;38(8):904-9
references: 16862161
references: Nat Genet. 2008 Feb;40(2):189-97
references: 18193044
references: Diabetes. 2008 Nov;57(11):3112-21
references: 18678614
references: Science. 2005 Sep 30;309(5744):2232-4
references: 16195467
references: Science. 2009 Sep 4;325(5945):1246-50
references: 19644074
references: Nat Genet. 2008 Jun;40(6):716-8
references: 18454146
references: PLoS Biol. 2008 May 6;6(5):e107
references: 18462017
references: PLoS Genet. 2010 Apr 01;6(4):e1000888
references: 20369019
references: Genome Res. 2008 May;18(5):706-16
references: 18347327
references: Histochem Cell Biol. 2006 Sep;126(3):335-42
references: 16521002