Skip to main content
SpringerLink
Log in

A review of major Crohn’s disease susceptibility genes and their role in disease pathogenesis

  • Review
  • Published:
Genes & Genomics Aims and scope Submit manuscript

Abstract

Crohn’s disease (CD) is a chronic inflammatory bowel disease whose relevance is increasing in industrialized society. Recent genome wide association studies revealed over seventy one loci associated with disease penetrance. Several variants that increase disease risk encode for altered proteins that diminish bacterial host defense. NOD2 alters intracellular bacterial sensing while ATG16L1 is thought to diminish bacterial clearance by impairing autophagy. Additionally, changes in the IBD5 locus are thought to diminish barrier function. Alternatively, recent data indicate a gain of function genetic variant of IL23R is protective amongst European CD patients. These recent genetic discoveries contradict historical theories that Crohn’s disease results from overactive auto-aggressive responses. Rather, new genetic data suggest disease-associated variants encode for dysfunctional proteins that diminish essential innate immune responses against commensal organisms. This review provides an overview of these critical discoveries and places them in their biological context.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Barrett JC, Hansoul S, Nicolae DL, Cho JH, Duerr RH, Rioux JD et al. (2008) Genome-wide association defines more than 30 distinct susceptibility loci for Crohn’s disease. Nat. Gen. 40: 955–962

    Article  CAS  Google Scholar 

  • Berg DJ, Davidson N, Kühn R, Müller W, Menon S, Holland G, Thompson-Snipes L, Leach MW, Rennick D (1996) Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4(+) TH1-like responses. J. Clin. Invest. 98: 1010–1020.

    Article  PubMed  CAS  Google Scholar 

  • Beutler B (2001) Autoimmunity and Apoptosis: the Crohn’s connection. Immunity 15: 5–14.

    Article  PubMed  CAS  Google Scholar 

  • Brand S (2009) Crohn’s disease: Th1, Th17 or both? The change of a paradigm: new immunological and genetic insights implicate Th17 cells in the pathogenesis of Crohn’s disease. Gut. 58:1152–1167.

    Article  PubMed  CAS  Google Scholar 

  • Burckhardt G and Wolff N. (2000) Structure of renal organic anion and cation transporters. Am. J. Physiol. Renal. Physiol. 278: 853–866.

    Google Scholar 

  • Cadwell K (2010) Crohn’s Disease Susceptibility Gene Interactions, a NOD to the Newcomer ATG16L1. Gastroenterology. 139: 1448–1450.

    Article  PubMed  Google Scholar 

  • Cadwell K, Liu JY, Brown SL, Miyoshi H, Loh J, et al. (2008) A key role for autophagy and the autophagy gene Atg16l1 in mouse and human intestinal Paneth cells. Nature 456: 259–263

    Article  PubMed  Google Scholar 

  • Cadwell K, Patel KK, Komatsu M, Virgin HW 4th & Stappenbeck, TS (2009) A common role for Atg16L1, Atg5 and Atg7 in small intestinal Paneth cells and Crohn’s disease. Autophagy 5: 250–252.

    Article  PubMed  CAS  Google Scholar 

  • Cadwell K, Patel K, Maloney N, Liu TC, NG A, Storer C, Head R, Xavier R, Stappenbeck T, and Virgin H. (2010) Virus-Plus-Susceptibility Gene Interaction Determines Crohn’s Disease Gene Atg16L1 Phenotypes in Intestine. Cell 141: 1135–1145.

    Article  PubMed  CAS  Google Scholar 

  • Church J (2001) Molecular Genetics and Crohn’s Disease. Surgical Clinics of North America 81.

  • Cotterill L, Payne D, Levinson S, McLaughlin J, Wesley E, Feeney M, Durbin H, Lal S, Makin A, Campbell S, et al. (2010) Replication and meta-analysis of 13,000 cases defines the risk for interleukin-23 receptor and autophagy-related 16-like 1 variants in Crohn’s disease. J Gastroenterol 24: 297–302.

    Google Scholar 

  • Csöngei V, Járomi L, Sáfrány E, Sipeky C, Magyari L, Faragó B, Bene J, Polgár N, Lakner L, Sarlós P (2010) Interaction of the major inflammatory bowel disease susceptibility alleles in Crohn’s disease patients. World. J. Gastroenterol. 16: 176–183.

    Article  PubMed  CAS  Google Scholar 

  • Deretic V, Master S, and Singh S (2008) Autophagy gives a nod and a wink to the inflammasome and Paneth cells in Crohn’s disease. Dev. Cell. 15; 641–642.

    Article  PubMed  CAS  Google Scholar 

  • Duerr R et al. (2006) A Genome-Wide Association Study Identifies IL23R as an Inflammatory Bowel Disease Gene. Science 314: 1461–1463.

    Article  PubMed  CAS  Google Scholar 

  • Duerr R (2007) Genome-Wide Association Studies Herald a New Era of Rapid Discoveries in Inflammatory Bowel Disease Research. Gastroenterology 132: 2045–2062.

    Article  PubMed  CAS  Google Scholar 

  • Eckburg PB, Bik EM, Bernstein CN, Purdom E, Dethlefsen L, Sargent M, Gill SR, Nelson KE, Relman DA (2005) Diversity of the human intestinal microbial flora. Science 308: 1635–1638.

    Article  PubMed  Google Scholar 

  • Einarsdottir E, Koskinen LL, Dukes E, Kainu K, Suomela S, Lappalainen M, Ziberna F, Korponay-Szabo IR, Kurppa K, Kaukinen K, et al. (2009) IL23R in the Swedish, Finnish, Hungarian and Italian populations: association with IBD and psoriasis, and linkage to celiac disease. BMC Med. Genet. 10: 8.

    Article  PubMed  CAS  Google Scholar 

  • Elson CO, Cong Y, Weaver CT, Schoeb TR, McClanahan TK, Fick RB, Kastelein RA. (2007) Monoclonal anti-interleukin 23 reverses active colitis in a T cell-mediated model in mice. Gastroenterology 132: 2359–2370.

    Article  PubMed  CAS  Google Scholar 

  • Fedorak RN and Dieleman LA. (2008) Probiotics in the treatment of human inflammatory bowel diseases. J. Clin. Gastroenterol. 42: 97–103.

    Article  Google Scholar 

  • Fernando MM, Stevens CR, Walsh EC, De Jager PL, Goyette P, et al. (2008) Defining the role of the MHC in autoimmunity: a review and pooled analysis. PloS Genet. 4:e1000024

    Article  PubMed  CAS  Google Scholar 

  • Fisher SA, Tremelling M, Anderson CA, Gwilliam R, Bumpstead S, et al. (2008) Genetic determinants of ulcerative colitis include the ECM1 locus and five loci implicated in Crohn’s disease. Nat. Genet. 40:710–712.

    Article  PubMed  CAS  Google Scholar 

  • Franke A, McGovern DP, Barrett JC, Wang K, Radford-Smith GL, Ahmad T, Lees CW, Balschun T, Lee J, Roberts R, et al (2010) Genome-wide meta-analysis increases to 71 the number of confirmed Crohn’s disease susceptibility loci. Nat. Gen. 42:1118–1125.

    Article  CAS  Google Scholar 

  • Fransen K, Visschedijk M, Sommeren S, Fu J, Franke L, Festen E, Stokkers P, Bodegrave A, Crusius V, Hommes D, et al. (2010) Analysis of SNPs with an effect on gene expression identifies UBE2L3 and BCL3 as potential new risk genes for Crohn’s disease. Hum. Mol. Genet. 19: 3482–3488.

    Article  PubMed  CAS  Google Scholar 

  • Fritz T, Niederreiter L, Adoph T, Blumberg R, and Kaser A. (2011) Crohn’s disease: NOD2, autophagy and ER stress converge. Gut. doi:10.1136/gut.2009.206466

  • Fujita N, Saitoh T, Kageyama S, Akira S, Noda T, and Yoshimori T. (2009) Differential involvement of Atg16L1 in Crohn disease and canonical autophagy: analysis of the organization of the Atg16L1 complex in fibroblasts. J. Biol. Chem. 284: 32602–32609.

    Article  PubMed  CAS  Google Scholar 

  • Glas J, Seiderer J, Wetzke M, Konrad A, Török HP, Schmechel S, Tonenchi L, Grassl C, Dambacher J, Pfennig S, et al. (2007) rs1004819 is the main disease-associated IL23R variant in German Crohn’s disease patients: combined analysis of IL23R, CARD15, and OCTN1/2 variants. PLoS One 2: e819.

    Article  PubMed  CAS  Google Scholar 

  • Glas J, Konrad A, Schmechel S, Dambacher J, Seiderer J, Schroff F, Wetzke M, Roeske D, Török HP, Tonenchi L, et al. (2008) The ATG16L1 gene variants rs2241879 and rs2241880 (T300A) are strongly associated with susceptibility to Crohn’s disease in the German population. Am J Gastroenterol 103: 682–691.

    Article  PubMed  CAS  Google Scholar 

  • Hamm CM, Reimers MA, McCullough CK, Gorbe EB, Lu J, Gu CC, Li E, Dieckgraefe BK, Gong Q, Stappenbeck, TS. (2010) NOD2 status and human ileal gene expression. Inflamm. Bowel. Dis. 16: 1649–1657.

    Article  PubMed  Google Scholar 

  • Hampe J, Franke A, Rosenstiel P, Till A, Teuber M, et al. (2007) A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn’s disease in ATG16L1. Nat. Genet. 39: 207–211.

    Article  PubMed  CAS  Google Scholar 

  • Hildebrandt MA, Hoffmann C, Sherrill-Mix SA, Keilbaugh SA, Hamady M, Chen YY, Knight R, Ahima RS, Bushman F, and Wu GD (2009) High-fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology 137: 1716-24.e1–1716-24.e2.

    Article  CAS  Google Scholar 

  • Hradsky O, Dusatkova P, Lenicek M, Bronsky J, Duricova D, Nevoral J, Vitek L, Lukas M, and Cinek O. (2010) Two Independent Genetic Factors Responsible for the Associations of the IBD5 Locus with Crohn’s Disease in the Czech Population. Inflamm. Bowel. Dis. 1–7.

  • Hu C, Sun L, Hu Y, Lu D, Wang H, Tang S. (2010) Functional characterization of the NF-kappaB binding site in the human NOD2 promoter. Cell. Mol. Immuno. 7: 288–295. Epub 2010 May 3.

    Article  CAS  Google Scholar 

  • Hue S, Ahern P, Buonocore S, Kullberg MC, Cua DJ, McKenzie BS, Powrie F, Maloy KJ (2006) Interleukin-23 drives innate and T cell-mediated intestinal inflammation. J. Exp. Med. 203: 2473–2483.

    Article  PubMed  CAS  Google Scholar 

  • Hugot J, Chamaillard M, Zoual H, Lesage S, Cezard J, Belaiche J, Almer S, Tysk C, O’Morain C, Gassull M, et al. (2001) Association of NOD2 leucine rich repeat variants with susceptibility to Crohn’s Disease. Nature 411: 599–603.

    Article  PubMed  CAS  Google Scholar 

  • Hugot J, Zouali H, and Lesage, S (2003) Lessons to be learned from the NOD2 gene in Crohn’s Disease. Eur. J. Gastroenterol. Hepatol. 15: 593–597.

    Article  PubMed  CAS  Google Scholar 

  • Hugot J, Chamaillar, M, Zouali H, Lesage S, Cezard J, Belaiche J, Almer S, Tysk C, O’Morain C, Gassull M, et al. (2009) Association of NOD2 leucine rich repeat variants with susceptibility to Crohn’s Disease. Nature 411: 599–603.

    Article  CAS  Google Scholar 

  • Karlinger K, Györke T, Makö E, Mester A, Tarján Z (2000) The epidemiology and the pathogenesis of inflammatory bowel disease. Eur. J. Radiol. 35: 154–167.

    Article  PubMed  CAS  Google Scholar 

  • Kim Y, Park J and Shaw M et al. (2008) The cytosolic sensors Nod1 and Nod2 are critical for bacterial recognition and host defense after exposure to Toll-like receptor ligands, Immunity 28: 246–257.

    Article  PubMed  CAS  Google Scholar 

  • Kobayashi T, Okamoto S, Hisamatsu T, Kamada N, Chinen H, Saito R, Kitazume M, Nakazawa A, Sugita A, Koganei K, Isobe K, and Hibi T. (2008) IL23 differentially regulates, the TH1/TH17 balance in ulcerative colitis and Crohn’s disease. Gut 57: 1682–1689.

    Article  PubMed  CAS  Google Scholar 

  • Kosovac K, Brenmoehl J, Hller E, Falk W, Schoelmerich J, Hausmann M & Rogler G. (2010) Association of the NOD2 genotype with bacterial translocation via altered cell-cell contacts in Crohn’s disease patients. Inflamm. Bowel. Dis. 16: 1311–1321.

    PubMed  Google Scholar 

  • Kuballa P, Huett A, Rioux JD, Daly MJ, Xavier RJ (2008) Impaired autophagy of an intracellular pathogen induced by a Crohn’s disease associated ATG16L1 variant. PLos ONE 3:e3391

    Article  PubMed  CAS  Google Scholar 

  • Kullberg MC, Jankovic D, Feng CG, Hue S, Gorelick PL, McKenzie BS, Cua DJ, Powrie F, Cheever AW, Maloy KJ, et al. (2006). IL-23 plays a key role in Helicobacter hepaticus-induced T cell-dependent colitis. J. Exp. Med. 203: 2485–2494.

    Article  PubMed  CAS  Google Scholar 

  • Lacher M, Schroepf S, Helmbrecht J, von Schweinitz D, Ballauff A, Koch I, Lohse P, Osterrieder S, Kappler R, Koletzko S (2010) Association of the interleukin-23 receptor gene variant rs11209026 with Crohn’s disease in German children. Acta. Paediatr. 99: 727–733.

    PubMed  CAS  Google Scholar 

  • Lakatos P, Szamosi T, Szilvasi A, Molnar E, Lakatos L, Kovacs A, Molnar T, Altorjay I, Papp M, Tulassay Z, et al. (2008) ATG16L1 and IL23 receptor (IL23R) genes are associated with disease susceptibility in Hungarian CD patients. Dig. Liver. Dis. 40: 867–873.

    Article  PubMed  CAS  Google Scholar 

  • Lecat A, Piette J, Legrand-Poels S (2010) The protein NOD2: an innate receptor more complex than previously assumed. Biochem. Pharmacol. 80: 2021–2031.

    Article  PubMed  CAS  Google Scholar 

  • Lee JC and Parkes M (2011) Genome-wide association studies and Crohn’s disease. Brief. Funct. Genomics. 10: 71–76.

    Article  PubMed  CAS  Google Scholar 

  • Levine, B (2005) Eating oneself and Univited Guests: Autophagy-Related Pathways in Cellular Defense. Cell 120: 159–162.

    PubMed  CAS  Google Scholar 

  • Loftus EV Jr. (2004) Clinical epidemiology of inflammatory bowel disease: incidence, prevalence and environmental influences. Gastroenterology 126:1504–1517.

    Article  PubMed  Google Scholar 

  • Lichtenstein GR, Hanauer SB, Sandborn WJ (2009) Practice Parameters Committee of the American college of gastroenterology. Am. J. Gastroenterol. 104: 465–483.

    Article  PubMed  Google Scholar 

  • Matthew C (2008) New links to the pathogenesis of Crohn disease provided by genome-wide association scans. Nat. Rev. Genet. 9: 9–14.

    Article  CAS  Google Scholar 

  • Matzinger P (2002) The danger model: a renewed sense of self. Science 296: 301–305.

    Article  PubMed  CAS  Google Scholar 

  • Maynard CL and Weaver CT (2009) Intestinal effector T cells in health and disease. Immunity 31: 389–400.

    Article  PubMed  CAS  Google Scholar 

  • McCarroll SA, Huett A, Kuballa P, Chilewski SD, Landry A, Goyette P, Zody MC, Hall JL, Brant SR, Cho JH, Duerr RH et al. (2008) Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn’s disease. Nat. Gen. 40: 1107–1112.

    Article  Google Scholar 

  • McGovern D, Rotter J, Mei L, Haritunians, T, Landers C, Derkowski C, Dutridge D, Dubinsky M, Ippoliti A, Vasiliauska, E et al. (2009) Genetic Epitasis of IL23/IL17 Pathway Genes in Crohn’s Disease. Inflamm. Bowel. Dis. 15: 883–889.

    Article  PubMed  Google Scholar 

  • Mitozugchi A and Mizoguchi E (2010) Animal Models of IBD: Linkage to human disease. Curr. Opin. Pharmacol. 10: 578–587.

    Article  CAS  Google Scholar 

  • Mizoguchi A, Ogawa A, Takedatsu H, Sugimoto K, Shimomura Y, Shirane K, Nagahama K, Nagaishi T, Mizoguchi E, Blumberg RS, et al. (2007) Dependence of intestinal granuloma formation on unique myeloid DC-like cells. J. Clin. Invest. 117: 605–615.

    Article  PubMed  CAS  Google Scholar 

  • Molodecky NA and Kaplan GG (2010) Environmental risk factors for inflammatory bowel disease. Gastroenterol. Hepatol. (N Y) 6: 339–346.

    Google Scholar 

  • Nell S, Suerbaum S and Josenhans C (2010). The impact of the microbiota on the pathogenesis of IBD. Nat. Rev. Microbiol. 8: 564–577.

    Article  PubMed  CAS  Google Scholar 

  • Newman WG, Zhang Q, Liu X, Amos CI, and Siminovitch KA (2009) Genetic variants in IL-23R and ATG16L1 independently predispose to increased susceptibility to Crohn’s disease in a Canadian population. J. Clin. Gastroenterol. 43: 444–447.

    Article  PubMed  CAS  Google Scholar 

  • Noble CL, Nimmo ER, Drummond H, et al. (2005). The contribution of OCTN1/2 variants within the IBD5 locus to disease susceptibility and severity in Crohn’s disease. Gastroenterology 129: 1854–1864.

    Article  PubMed  CAS  Google Scholar 

  • Noguchi E, Homma Y, Kang X, Netea M, and Ma X. (2009) A CD associated NOD2 mutation suppresses transcription of human IL10 by inhibiting activity of the nuclear ribonucleoprotein hnRNP-A1. Nat. Immunol. 10: 471–479.

    Article  PubMed  CAS  Google Scholar 

  • Ogura Y, Bonen DK, Inohara N et al. (2001). A frameshift mutation in NOD2 association with susceptibility to Crohn’s disease. Nature 411: 599–603.

    Article  CAS  Google Scholar 

  • Palomino-Morales, RJ, Gomez-Garcia, M, Lopez-Nevot, MA, Rodrigo, L, Nieto, A, Alizadeh, BZ, and Martin, J (2009) Association of ATG16L1 and IRGM genes polymorphisms with inflammatory bowel disease: a meta-analysis approach. Genes. Immun. 10: 356–364.

    Article  PubMed  CAS  Google Scholar 

  • Peltekova VD, Wintle RF, Rubin LA et al. (2004) Functional variants of OCTN cation transporter genes are associated with Crohn disease. Nat. Genet. 36: 471–475.

    Article  PubMed  CAS  Google Scholar 

  • Podolsky DK (2002) Inflammatory bowel disease. N Engl J Med 347: 417–429.

    Article  PubMed  CAS  Google Scholar 

  • Ramsay RR (2000) The carnitine acyltransferases: modulators of acyl-CoA-dependent reactions. Biochem. Soc. Trans. 28: 182–186.

    PubMed  CAS  Google Scholar 

  • Reinhard C and Rioux J (2006) Role of the IBD5 Susceptibility Locus in the Inflammatory Bowel Diseases. Inflamm. Bowel. Dis. 12: 227–238.

    Article  PubMed  Google Scholar 

  • Repnik K. and Potocniki U (2010) CTLA3 CT60 Single-Nucleotide Polymorphism is Associated with Slovenian Inflammatory Bowel Disease Patients and Regulates Expression of CTLA4 Isoforms. DNA Cell Biol 00: 1–8.

    Google Scholar 

  • Rioux JD, Silverberg MS, Daly MJ et al. (2000) Genomewide search in Canadian families with inflammatory bowel disease reveals two novel susceptibility loci. Am. J. Hum. Genet. 66: 1863–1870.

    Article  PubMed  CAS  Google Scholar 

  • Roediger W and Nance S (1986) Metabolic induction of experimental ulcerative colitis by inhibition of fatty acid oxidation. Br. J. Exp. Pathol. 67: 773–782.

    PubMed  CAS  Google Scholar 

  • Sabbah A, Chang TH, Harnack R, Frohlich V, Tominaga K, Dube PH, Xiang Y, and Bose S (2009) Activation of innate immune antiviral responses by Nod2. Nat. Immunol. 10: 1073–1080.

    Article  PubMed  CAS  Google Scholar 

  • Silverberg M, Duerr R, Brant S, Bromfield G, Datta L, Jani N, Kane S, Rotter J, Schumm P, Steinhart H, et al. (2007) Refined genomic localization and ethnic differences observed for the IBD5 association with Crohn’s disease. Eur. J. Hum. Genet. 15: 328–335.

    Article  PubMed  CAS  Google Scholar 

  • Singh SB, Davis AS, Taylor GA, and Deretic V (2006) Human IRGM induces autophagy to eliminate intracellular mycobacteria. Science 313: 1438–1441. Epub 2006 Aug 3.

    Article  PubMed  CAS  Google Scholar 

  • Stappenbeck T, Rioux J, Mizoguchi A, Saitoh T, Huett A, Darfeuille-Michaud A, Wileman T, Mizushim N, Carding S, Akira S, et al. (2010) Crohn Disease: A current Perspective on Genetics, Autophagy and Immunity. Autophagy 7: 1–20.

    Google Scholar 

  • Swoger JM and Binion, DG (2010) Supportive therapy in IBD: what additional diagnoses and conditions must be treated? Dig. Dis. 28: 452–462.

    Article  PubMed  Google Scholar 

  • Taylor KD, Targan SR, Mei L, Ippoliti AF, McGovern D, Mengesha E, King L, Rotter JI (2008) IL23R haplotypes provide a large population attributable risk for Crohn’s disease. Inflamm. Bowel. Dis. 14: 1185–1191.

    Article  PubMed  Google Scholar 

  • Tokuhiro S, Yamada R, Chang X, Suzuki A, Kochi Y, Sawada T, Suzuki M, Nagasaki m, Ohtsuki M, Ono M et al. (2003) An Intronic SNP in a RUNX1 binding site of SLC22A4, encoding an organic cation transporter, is associated with rheumatoid arthritis. Nat. Genet. 35: 341–348.

    Article  PubMed  CAS  Google Scholar 

  • Travassos LH, Carneiro LA, Ramjeet M, Hussey S, Kim YG, Magalhães JG, Yuan L, Soares F, Chea E, Le Bourhis L, et al. (2010). Nod1 and Nod2 direct autophagy by recruiting ATG16L1 to the plasma membrane at the site of bacterial entry. Nat. Immunol. 11: 55–62.

    Article  PubMed  CAS  Google Scholar 

  • Tysk C, Lindberg E, Järnerot G, and Flodérus-Myrhed B (1988) Ulcerative colitis and Crohn’s disease in an unselected population of monozygotic and dizygotic twins; A study of heritability and the influence of smoking. Gut 29: 990–996.

    Article  PubMed  CAS  Google Scholar 

  • Uhlig HH, McKenzie BS, Hue S, Thompson C, Joyce-Shaikh B, Stepankova R, Robinson N, Buonocore S, Tlaskalova-Hogenova H, Cua DJ, Powrie F (2006) Differential activity of IL-12 and IL-23 in mucosal and systemic innate immune pathology. Immunity 25: 309–318.

    Article  PubMed  CAS  Google Scholar 

  • van Heel DA, Fisher SA, Kirby A, Daly MJ, Rioux JD, et al. (2004) Inflammatory bowel disease susceptibility loci defined by genome scan meta-analysis of 1952 affected relative pairs. Hum. Mol. Genet. 13:763–770.

    Article  PubMed  CAS  Google Scholar 

  • Van Limbergen J, Russell RK, Nimmo ER, Drummond HE, Smith L, Anderson NH, Davies G, Gillett PM, McGrogan P, Weaver LT, et al. (2008) Autophagy gene ATG16L1 influences susceptibility and disease location but not childhood-onset in Crohn’s disease in Northern Europe. Inflamm. Bowel. Dis, 14: 338–346.

    Article  PubMed  Google Scholar 

  • Van Limbergen, J, Wilson, D, and Satsangi, J (2009) The Genetics of Crohn’s Disease. Annu. Rev. Genomics. Hum. Genet. 10; 89–116.

    Article  PubMed  CAS  Google Scholar 

  • Wang, K Zhang, H, Kugathasan, S, Annese, V, Bradfield, J, Russel, R, Sleiman, P, Imielinski, M, Glessner, J, Hou, C, et al. (2009) Diverse Genome-wide Association Studies Associate the IL12/IL23 Pathway with Crohn Disease. Am. J. Hum.Genet. 84: 399–405.

    Article  PubMed  CAS  Google Scholar 

  • Xavier R and Podolsky DK (2005) Commensal flora: wolf in sheep’s clothing. Gastroenterology 128: 1122–1126.

    Article  PubMed  CAS  Google Scholar 

  • Xavier RJ and Podolsky DK (2007). Unravelling the pathogenesis of inflammatory bowel disease. Nature 448: 427–434.

    Article  PubMed  CAS  Google Scholar 

  • Xavier R (2008) Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn’s disease. Nat. Gen. 4: 1107–1112.

    Google Scholar 

  • Zenhzhirong C, Xiaoqin W, Minhu C, Mei L, Xiang G, Baili C, and Pinjin H (2009) Contribution of rs11465788 in IL23R gene to Crohn’s disease susceptibility and phenotype in Chinese population. J.Genet 88: 191–196.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dept of Biological, Chemical and Physical Sciences, Roosevelt University, Chicago, USA

    Meghan Barrett & Sathees B. Chandra

Authors
  1. Meghan Barrett
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sathees B. Chandra
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sathees B. Chandra.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Barrett, M., Chandra, S.B. A review of major Crohn’s disease susceptibility genes and their role in disease pathogenesis. Genes Genom 33, 317–325 (2011). https://doi.org/10.1007/s13258-011-0076-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13258-011-0076-3

Keywords

Search

Navigation