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Peloquin JM, Goel G, Kong L, et al. Characterization of candidate genes in inflammatory bowel disease-associated risk loci. JCI Insight. 2016;1(13):e87899doi: 10.1172/jci.insight.87899.
Peloquin, J. M., Goel, G., Kong, L., Huang, H., Haritunians, T., Sartor, R. B., Daly, M. J., Newberry, R. D., McGovern, D. P., Yajnik, V., Lira, S. A., & Xavier, R. J. (2016). Characterization of candidate genes in inflammatory bowel disease-associated risk loci. JCI insight, 1(13), e87899. https://doi.org/10.1172/jci.insight.87899
Peloquin, Joanna M, et al. "Characterization of candidate genes in inflammatory bowel disease-associated risk loci." JCI insight vol. 1,13 (2016): e87899. doi: https://doi.org/10.1172/jci.insight.87899
Peloquin JM, Goel G, Kong L, Huang H, Haritunians T, Sartor RB, Daly MJ, Newberry RD, McGovern DP, Yajnik V, Lira SA, Xavier RJ. Characterization of candidate genes in inflammatory bowel disease-associated risk loci. JCI Insight. 2016 Aug 18;1(13):e87899. doi: 10.1172/jci.insight.87899. PMID: 27668286; PMCID: PMC5033062.
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JCI Insight. 2016 Aug 18;1(13):e87899. doi: 10.1172/jci.insight.87899.

Characterization of candidate genes in inflammatory bowel disease-associated risk loci.

JCI insight

Joanna M Peloquin, Gautam Goel, Lingjia Kong, Hailiang Huang, Talin Haritunians, R Balfour Sartor, Mark J Daly, Rodney D Newberry, Dermot P McGovern, Vijay Yajnik, Sergio A Lira, Ramnik J Xavier

Affiliations

  1. Gastrointestinal Unit and Center for the Study of Inflammatory Bowel Disease.
  2. Center for Computational and Integrative Biology.
  3. Analytic and Translational Genetics Unit, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
  4. Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
  5. F. Widjaja Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
  6. Department of Medicine, Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
  7. Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri, USA.
  8. Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, New York, USA.

PMID: 27668286 PMCID: PMC5033062 DOI: 10.1172/jci.insight.87899

Abstract

GWAS have linked SNPs to risk of inflammatory bowel disease (IBD), but a systematic characterization of disease-associated genes has been lacking. Prior studies utilized microarrays that did not capture many genes encoded within risk loci or defined expression quantitative trait loci (eQTLs) using peripheral blood, which is not the target tissue in IBD. To address these gaps, we sought to characterize the expression of IBD-associated risk genes in disease-relevant tissues and in the setting of active IBD. Terminal ileal (TI) and colonic mucosal tissues were obtained from patients with Crohn's disease or ulcerative colitis and from healthy controls. We developed a NanoString code set to profile 678 genes within IBD risk loci. A subset of patients and controls were genotyped for IBD-associated risk SNPs. Analyses included differential expression and variance analysis, weighted gene coexpression network analysis, and eQTL analysis. We identified 116 genes that discriminate between healthy TI and colon samples and uncovered patterns in variance of gene expression that highlight heterogeneity of disease. We identified 107 coexpressed gene pairs for which transcriptional regulation is either conserved or reversed in an inflammation-independent or -dependent manner. We demonstrate that on average approximately 60% of disease-associated genes are differentially expressed in inflamed tissue. Last, we identified eQTLs with either genotype-only effects on expression or an interaction effect between genotype and inflammation. Our data reinforce tissue specificity of expression in disease-associated candidate genes, highlight genes and gene pairs that are regulated in disease-relevant tissue and inflammation, and provide a foundation to advance the understanding of IBD pathogenesis.

Conflict of interest statement

The authors declare that no conflict of interest exists.

References

  1. Immunity. 2016 Jun 21;44(6):1392-405 - PubMed
  2. Nat Biotechnol. 2008 Mar;26(3):317-25 - PubMed
  3. Mucosal Immunol. 2014 Nov;7(6):1312-25 - PubMed
  4. PLoS Genet. 2015 May 08;11(5):e1005223 - PubMed
  5. J Clin Invest. 2014 Aug;124(8):3617-33 - PubMed
  6. Nat Genet. 2012 Oct;44(10):1084-9 - PubMed
  7. Nat Rev Genet. 2013 Sep;14(9):661-73 - PubMed
  8. Inflamm Bowel Dis. 2009 Feb;15(2):224-35 - PubMed
  9. BMC Genomics. 2015 Feb 27;16:138 - PubMed
  10. Immunity. 2013 May 23;38(5):970-83 - PubMed
  11. Gut. 2016 Feb;65(2):256-70 - PubMed
  12. PLoS Genet. 2013 May;9(5):e1003487 - PubMed
  13. BMC Syst Biol. 2007 Nov 21;1:54 - PubMed
  14. Nat Commun. 2013;4:2112 - PubMed
  15. Nat Med. 2016 Jun;22(6):598-605 - PubMed
  16. J Crohns Colitis. 2014 Aug;8(8):845-51 - PubMed
  17. PLoS Genet. 2011 Aug;7(8):e1002207 - PubMed
  18. Science. 2015 May 8;348(6235):660-5 - PubMed
  19. Gastroenterology. 2013 Jun;144(7):1488-96, 1496.e1-3 - PubMed
  20. Biochim Biophys Acta. 2014 Oct;1842(10):1896-1902 - PubMed
  21. Nature. 2012 Nov 1;491(7422):119-24 - PubMed
  22. Clin Transl Gastroenterol. 2014 Mar 20;5:e55 - PubMed
  23. Cell Host Microbe. 2012 Feb 16;11(2):140-52 - PubMed
  24. Nucleic Acids Res. 2014 Jan;42(Database issue):D1001-6 - PubMed
  25. Am J Clin Nutr. 2016 Jul;104(1):113-20 - PubMed
  26. Am J Physiol Gastrointest Liver Physiol. 2015 Sep 1;309(5):G341-9 - PubMed
  27. PLoS Genet. 2016 Mar 25;12(3):e1005908 - PubMed
  28. Gut. 2008 Oct;57(10):1398-405 - PubMed
  29. BMC Med Genomics. 2014 Jun 03;7:31 - PubMed
  30. Clin Ther. 2015 May 1;37(5):996-1009.e7 - PubMed
  31. J Virol. 2002 Nov;76(21):11133-8 - PubMed
  32. PLoS Comput Biol. 2015 May 13;11(5):e1004220 - PubMed
  33. Hum Mol Genet. 2015 Jul 15;24(14):4147-57 - PubMed
  34. Autophagy. 2016 Jun 2;12(6):1057-8 - PubMed
  35. PLoS Genet. 2012 Jan;8(1):e1002431 - PubMed
  36. Eur J Hum Genet. 2011 Nov;19(11):1173-80 - PubMed
  37. FEBS J. 2014 Jan;281(1):216-31 - PubMed
  38. Nutrients. 2013 Sep 27;5(10):3898-909 - PubMed
  39. Gut. 2015 Jul;64(7):1082-94 - PubMed
  40. Clin Exp Immunol. 2009 Apr;156(1):161-71 - PubMed
  41. PLoS One. 2009 Jun 15;4(6):e5921 - PubMed
  42. Nat Rev Immunol. 2014 Oct;14(10):667-85 - PubMed
  43. BMC Bioinformatics. 2010 Oct 06;11:497 - PubMed
  44. Inflamm Bowel Dis. 2011 Oct;17(10):2205-6 - PubMed
  45. Inflamm Bowel Dis. 2010 Oct;16(10):1717-28 - PubMed
  46. Biochim Biophys Acta. 2006 Mar;1762(3):341-50 - PubMed
  47. Leuk Res. 2010 Mar;34(3):289-93 - PubMed
  48. Nat Immunol. 2012 Jul 01;13(8):770-7 - PubMed
  49. Nat Genet. 2012 Mar 25;44(5):502-10 - PubMed
  50. Science. 2014 Mar 7;343(6175):1246949 - PubMed
  51. Nat Genet. 2013 Jun;45(6):580-5 - PubMed
  52. Science. 2014 Mar 7;343(6175):1246980 - PubMed
  53. Nat Commun. 2015 May 08;6:6821 - PubMed
  54. PLoS One. 2009 Nov 24;4(11):e7984 - PubMed
  55. Nat Immunol. 2008 Oct;9(10):1091-4 - PubMed
  56. Immunity. 2015 Oct 20;43(4):739-50 - PubMed
  57. Hum Mol Genet. 2015 Oct 1;24(19):5619-27 - PubMed
  58. Inflamm Bowel Dis. 2015 Nov;21(11):2495-506 - PubMed
  59. Genes Brain Behav. 2014 Jan;13(1):13-24 - PubMed
  60. Nat Commun. 2015 Aug 10;6:7971 - PubMed
  61. Nat Immunol. 2010 Jun;11(6):471-6 - PubMed
  62. Nature. 2015 Feb 19;518(7539):337-43 - PubMed
  63. Toxicol In Vitro. 2004 Dec;18(6):749-54 - PubMed
  64. Ann Rheum Dis. 2015 Mar;74(3):e14 - PubMed
  65. Inflamm Bowel Dis. 2015 Feb;21(2):251-6 - PubMed
  66. Cell. 2015 Dec 3;163(6):1400-12 - PubMed
  67. Nat Genet. 2013 Oct;45(10):1238-43 - PubMed
  68. Proc Natl Acad Sci U S A. 2015 Sep 15;112(37):11618-23 - PubMed
  69. Science. 2014 May 2;344(6183):519-23 - PubMed

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