The Identification of Genes for Inflammatory Bowel Disease


Details of Research

Contact: Joanne Stempak, Project Manager
416-586-4800 ext 8399

Primary Investigator:
Mark Silverberg, MD
Enrolment: Ongoing

This initiative is funded by the National Institutes of Health in the United States and has allowed us to form an IBD Genetic Research Centre in order to build upon our previous efforts in this area.

Objective is to identify new genes and other biomarkers that may be responsible for causing Inflammatory Bowel Disease (IBD) and understand the role of previously identified biomarkers in IBD.

Expectation: This research will lead to a better understanding of why the disease occurs, easier diagnostic tools that may avoid the need for colonoscopies, better therapies or even a cure.

Eligibility: Anyone who has a confirmed diagnosis of IBD (either Crohn's Disease or Ulcerative Colitis). Also, if you do not have IBD (i.e. Crohn's Disease or ulcerative colitis) and do not have a family history of IBD and are willing to provide a blood sample as a healthy control, your help would be greatly appreciated.


  • Participation is very brief and involves providing us with:
    • Information regarding your family history and disease specifics
    • A small blood sample for genetic testing
    • Permission to review your medical information regarding IBD
  • You will not have to see any physicians at Mount Sinai Hospital


  • Those with a family history of IBD may be asked for permission to contact affected individuals to participate as well.
  • Those without a family history may also be asked for permission to contact parents or other unaffected relatives (even if they do NOT have IBD) to provide a blood sample.

Status Update:

Updated as of Fall 2012 by Joanne Stempak

Participant Tally:
6000 - this includes Crohn’s Disease and Ulcerative colitis patients, parents, siblings, other relatives, and non-IBD (healthy) controls.

Genetic Analysis / Results:
We are working with the samples that we have collected. This process takes a while and is ongoing. New findings are published in scientific research articles that are publicly available (link below). Below are the titles of some the research articles we have contributed to in this area.

We would like to sincerely thank all of our study participants. This research couldn't be possible without your cooperation.
Please contact Joanne Stempak (phone: 416-586-4800 x 8399) if any of the following applies to you:

Healthy Controls:
If you do not have IBD (i.e. Crohn's Disease or ulcerative colitis) and do not have a family history of IBD and are willing to provide a blood sample for this research, your help would be greatly appreciated.

You have a scheduled colonoscopy:
If you have an upcoming colonoscopy and you are willing to fill in a food diary for 4 days prior to your colonoscopy and are willing to provide a blood sample and/or tissue biopsies obtained during your procedure, please contact us. This research is being done to help understand the role of diet in IBD by studying its effect on the gut microbiome.

You are about to start Infliximab or Humira, for the first time:
If you are about to start medical treatment with Infliximab or Humira for the first time (and have not had previous surgeries or resections for IBD) and if you're willing to participate in a research study, please contact us. This study aims to identify the factors that may affect why some patients respond or don't respond to these medical therapies. The study follows you for a period of 28-30 weeks as your are seen by your doctor for your routine medical care. This study may involve extra biopsy collections during your regularly scheduled colonoscopies, with your permission.

a. Genetic Analysis of Infliximab-treated Inflammatory Bowel Disease Patients
Tumour necrosis factor-alpha blocking agents encompass some of the available therapies for Inflammatory Bowel Disease patients. Infliximab is one of the most popular and effective amongst them and is used in both Crohn’s Disease and Ulcerative colitis. Studies show that the majority of Inflammatory Bowel Disease patients undergoing Infliximab therapy experience beneficial effects from the drug. Nevertheless, a small number of patients experience moderate to severe adverse effects to Infliximab infusions. The potential risk for patients and the high cost of Infliximab therapy demand further research into the factors pertaining to therapy response. To date, there are no reliable predictors of Infliximab therapy outcome. With this study, we aim to identify differentially expressed genes between responders and non-responders to Infliximab therapy and to examine if significant gene expression differences exist between Infliximab-treated Ulcerative colitis and Crohn’s Disease patients.

We are looking for individuals who have Crohn’s Disease or Ulcerative colitis who will be starting Infliximab treatment in the near future. For this study, please contact Joanne Stempak (phone: 416-586-4800 x 8399).

b. Mechanisms of Intestinal Inflammation Following Ileal Resection for Crohn's Disease
For many Crohn's Disease patients with small portions of severely affected terminal ileum, surgical removal of the diseased bowel and reconnection of the two ends is considered a reasonable treatment option. However, patients may experience recurrence of their disease in the future following surgery. Similar to hypotheses regarding the development of Crohn’s Disease, those relating to the recurrence of inflammation following surgery suggest that inflammation is the result of altered immunity in genetically predisposed individuals due to a combination of changes in gene expression and the microbial milieu. The aim of this study is to evaluate microbial and gene expression factors which are associated with the recurrence of small bowel inflammation following surgery for CD. This will have practical implications for evaluating which patients are more likely to rapidly recur as well as provide insight into the pathogenesis of Crohn’s Disease.

We are looking for individuals who have Crohn’s Disease and are planning to undergo Ileal Resection. For this study, please contact Joanne Stempak (phone: 416-586-4800 x 8399).

Click on the underlined links to read the abstract summaries.

  1. Rivas MA, Beaudoin M, Gardet A, Stevens C, Sharma Y, Zhang CK, Boucher G, Ripke S, Ellinghaus D, Burtt N, Fennell T, Kirby A, Latiano A, Goyette P, Green T, Halfvarson J, Haritunians T, Korn JM, Kuruvilla F, Lagacé C, Neale B, Lo KS, Schumm P, Törkvist L; National Institute of Diabetes and Digestive Kidney Diseases Inflammatory Bowel Disease Genetics Consortium (NIDDK IBDGC); United Kingdom Inflammatory Bowel Disease Genetics Consortium; International Inflammatory Bowel Disease Genetics Consortium, Dubinsky MC, Brant SR, Silverberg MS, Duerr RH, Altshuler D, Gabriel S, Lettre G, Franke A, D'Amato M, McGovern DP, Cho JH, Rioux JD, Xavier RJ, Daly MJ. Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease. Nat Genet. 2011 Oct 9;43(11):1066-73.

  2. Muise AM, Xu W, Guo CH, Walters TD, Wolters VM, Fattouh R, Lam GY, Hu P, Murchie R, Sherlock M, Gana JC; NEOPICS, Russell RK, Glogauer M, Duerr RH, Cho JH, Lees CW, Satsangi J, Wilson DC, Paterson AD, Griffiths AM, Silverberg MS, Brumell JH. NADPH oxidase complex and IBD candidate gene studies: identification of a rare variant in NCF2 that results in reduced binding to RAC2. Gut. 2011 Sep 7. [Epub ahead of print]

  3. Waterman M, Xu W, Stempak JM, Milgrom R, Bernstein CN, Griffiths AM, Greenberg GR, Steinhart AH, Silverberg MS. Distinct and overlapping genetic loci in Crohn’s disease and ulcerative colitis: Correlations with pathogenesis. Inflamm Bowel Dis. 2011 Sep;17(9):1936-42. 2010 Dec 10. [Epub ahead of print]

  4. Franke A, McGovern DP, Barrett JC, Wang K, Radford-Smith GL, Ahmad T, Lees CW, Balschun T, Lee J, Roberts R, Anderson CA, Bis JC, Bumpstead S, Ellinghaus D, Festen EM, Georges M, Green T, Haritunians T, Jostins L, Latiano A, Mathew CG, Montgomery GW, Prescott NJ, Raychaudhuri S, Rotter JI, Schumm P, Sharma Y, Simms LA, Taylor KD, Whiteman D, Wijmenga C, Baldassano RN, Barclay M, Bayless TM, Brand S, Büning C, Cohen A, Colombel JF, Cottone M, Stronati L, Denson T, De Vos M, D'Inca R, Dubinsky M, Edwards C, Florin T, Franchimont D, Gearry R, Glas J, Van Gossum A, Guthery SL, Halfvarson J, Verspaget HW, Hugot JP, Karban A, Laukens D, Lawrance I, Lemann M, Levine A, Libioulle C, Louis E, Mowat C, Newman W, Panés J, Phillips A, Proctor DD, Regueiro M, Russell R, Rutgeerts P, Sanderson J, Sans M, Seibold F, Steinhart AH, Stokkers PC, Torkvist L, Kullak-Ublick G, Wilson D, Walters T, Targan SR, Brant SR, Rioux JD, D'Amato M, Weersma RK, Kugathasan S, Griffiths AM, Mansfield JC, Vermeire S, Duerr RH, Silverberg MS, Satsangi J, Schreiber S, Cho JH, Annese V, Hakonarson H, Daly MJ, Parkes M. Genome-wide meta-analysis increases to 71 the number of confirmed Crohn’s disease susceptibility loci. Nat Genet. 2010 Dec;42(12):1118-25.

  5. Kabakchiev B, Turner D, Hyams J, Mack D, Leleiko N, Crandall W, Markowitz J, Otley AR, Xu W, Hu P, Griffiths AM, Silverberg MS. Gene expression changes associated with resistance to intravenous corticosteroid therapy in children with severe ulcerative colitis. PLoS One. 2010 Sep 30;5(9). pii: e13085.

  6. McGovern DP, Gardet A, Törkvist L, Goyette P, Essers J, Taylor KD, Neale BM, Ong RT, Lagacé C, Li C, Green T, Stevens CR, Beauchamp C, Fleshner PR, Carlson M, D'Amato M, Halfvarson J, Hibberd ML, Lördal M, Padyukov L, Andriulli A, Colombo E, Latiano A, Palmieri O, Bernard EJ, Deslandres C, Hommes DW, de Jong DJ, Stokkers PC, Weersma RK; NIDDK IBD Genetics Consortium, Sharma Y, Silverberg MS, Cho JH, Wu J, Roeder K, Brant SR, Schumm LP, Duerr RH, Dubinsky MC, Glazer NL, Haritunians T, Ippoliti A, Melmed GY, Siscovick DS, Vasiliauskas EA, Targan SR, Annese V, Wijmenga C, Pettersson S, Rotter JI, Xavier RJ, Daly MJ, Rioux JD, Seielstad M. Genome-wide association identifies multiple ulcerative colitis susceptibility loci. Nat Genet. 2010 Apr;42(4):332-7.

  7. Villani AC, Lemire M, Louis E, Silverberg MS, Collette C, Fortin G, Nimmo ER, Renaud Y, Brunet S, Libioulle C, Belaiche J, Bitton A, Gaudet D, Cohen A, Langelier D, Rioux JD, Arnott ID, Wild GE, Rutgeerts P, Satsangi J, Vermeire S, Hudson TJ, Franchimont D. Genetic variation in the familial Mediterranean fever gene (MEFV) and risk for Crohn's disease and ulcerative colitis. PLoS One. 2009 Sep 28;4(9):e7154.

  8. Bhat M, Nguyen GC, Pare P, Lahaie R, Deslandres C, Bernard EJ, Aumais G, Jobin G, Wild G, Cohen A, Langelier D, Brant S, Dassopoulos T, McGovern D, Torres E, Duerr R, Regueiro M, Silverberg MS, Steinhart H, Griffiths AM, Elkadri A, Cho J, Proctor D, Goyette P, Rioux J, Bitton A. Phenotypic and genotypic characteristics of inflammatory bowel disease in French Canadians: comparison with a large North American repository. Am J Gastroenterol. 2009 Sep;104(9):2233-40

  9. Muise AM, Walters TD, Glowacka WK, Griffiths AM, Ngan BY, Lan H, Xu W, Silverberg MS, Rotin D. Polymorphisms in E-cadherin (CDH1) result in a mis-localised cytoplasmic protein that is associated with Crohn's disease. Gut. 2009 Aug;58(8):1121-7.

  10. Festen EA, Goyette P, Scott R, Annese V, Zhernakova A, Lian J, Lefèbvre C, Brant SR, Cho JH, Silverberg MS, Taylor KD, de Jong DJ, Stokkers PC, Mcgovern D, Palmieri O, Achkar JP, Xavier RJ, Daly MJ, Duerr RH, Wijmenga C, Weersma RK, Rioux JD. Genetic variants in the region harbouring IL2/IL21 associated with ulcerative colitis. Gut. 2009 Jun;58(6):799-804.

  11. Silverberg MS, Cho JH, Rioux JD, McGovern DPB, Wu J, Annese V, Achkar JP, Goyette P, Scott R, Xu W, Barmada MM, Klei L, Daly MJ, Abraham C, Bayless TM, Bossa F, Griffiths AM, Ippoliti AF, Lahaie RG, Latiano A, Paré P, Proctor DD, Regueiro MD, Steinhart AH, Targan SR, Schumm LP, Kistner EO, Lee AT, Gregersen PK, Rotter JI, Brant SR, Taylor KD, Roeder K, Duerr RH. Ulcerative colitis-linked loci on chromosomes 1p36 and 12q15 found by genome-wide association study. Nature Genetics 2009 Feb;41(2):216-20.

  12. Villani AC, Lemire M, Fortin G, Louis E, Silverberg MS, Collette C, Baba N, Libioulle C, Belaiche J, Bitton A, Gaudet D, Cohen A, Langelier D, Fortin PR, Wither JE, Sarfati M, Rutgeerts P, Rioux JD, Vermeire S, Hudson TJ, Franchimont D. Common variants in the NLRP3 region contribute to Crohn's disease susceptibility. Nat Genet. 2009 Jan;41(1):71-6.

  13. Labbé C, Goyette P, Lefebvre C, Stevens C, Green T, Tello-Ruiz MK, Cao Z, Landry AL, Stempak J, Annese V, Latiano A, Brant SR, Duerr RH, Taylor KD, Cho JH, Steinhart AH, Daly MJ, Silverberg MS, Xavier RJ, Rioux JD. MAST3: a novel IBD risk factor that modulates TLR4 signaling. Genes Immun. 2008 Oct;9(7):602-12.

  14. McCarroll SA, Huett A, Kuballa P, Chilewski SD, Landry A, Goyette P, Zody MC, Hall JL, Brant SR, Cho JH, Duerr RH, Silverberg MS, Taylor KD, Rioux JD, Altshuler D, Daly MJ, Xavier RJ. Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn's disease. Nature Genetics 2008 Sep;40(9):1107-12.

  15. Barrett JC, Hansoul S, Nicolae DL, Cho JH, Duerr RH, Rioux JD, Brant SR, Silverberg MS, Taylor KD, Barmada MM, Bitton A, Dassopoulos T, Datta LW, Green T, Griffiths AM, Kistner EO, Murtha MT, Regueiro MD, Rotter JI, Schumm LP, Steinhart AH, Targan SR, Xavier RJ; NIDDK IBD Genetics Consortium, Libioulle C, Sandor C, Lathrop M, Belaiche J, Dewit O, Gut I, Heath S, Laukens D, Mni M, Rutgeerts P, Van Gossum A, Zelenika D, Franchimont D, Hugot JP, de Vos M, Vermeire S, Louis E; Belgian-French IBD Consortium; Wellcome Trust Case Control Consortium, Cardon LR, Anderson CA, Drummond H, Nimmo E, Ahmad T, Prescott NJ, Onnie CM, Fisher SA, Marchini J, Ghori J, Bumpstead S, Gwilliam R, Tremelling M, Deloukas P, Mansfield J, Jewell D, Satsangi J, Mathew CG, Parkes M, Georges M, Daly MJ. Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease. Nat Genet. 2008 Aug;40(8):955-62.

  16. Shugart YY, Silverberg MS, Duerr RH, Taylor KD, Wang MH, Zarfas K, Schumm LP, Bromfield G, Steinhart AH, Griffiths AM, Kane SV, Barmada MM, Rotter JI, Mei L, Bernstein CN, Bayless TM, Langelier D, Cohen A, Bitton A, Rioux JD, Cho JH, Brant SR. A SNP linkage scan identifies significant Crohn's disease loci on chromosomes 13q13.3 and, in Jewish families, on 1p35.2 and 3q29. Genes Immun. 2008 Mar;9(2):161-7.

  17. Goyette P, Lefebvre C, Ng A, Brant SR, Cho JH, Duerr RH, Silverberg MS, Taylor KD, Latiano A, Aumais G, Deslandres C, Jobin G, Annese V, Daly MJ, Xavier RJ, Rioux JD. Gene-centric association mapping of chromosome 3p implicates MST1 in IBD pathogenesis. Mucosal Immunol. 2008 Mar;1(2):131-8.
  18. Muise AM, Walters T, Wine E, Griffiths AM, Turner D, Duerr RH, Regueiro MD, Ngan BY, Xu W, Sherman PM, Silverberg MS, Rotin D. Protein-tyrosine phosphatase sigma is associated with ulcerative colitis. Curr Biol. 2007 Jul 17;17(14):1212-8. Epub 2007 Jul 5.
  19. De Jager PL, Franchimont D, Waliszewska A, Bitton A, Cohen A, Langelier D, Belaiche J, Vermeire S, Farwell L, Goris A, Libioulle C, Jani N, Dassopoulos T, Bromfield GP, Dubois B, Cho JH, Brant SR, Duerr RH, Yang H, Rotter JI, Silverberg MS, Steinhart AH, Daly MJ, Podolsky DK, Louis E, Hafler DA, Rioux JD; Quebec IBD Genetics Consortium; NIDDK IBD Genetics Consortium. The role of the Toll receptor pathway in susceptibility to inflammatory bowel diseases. Genes Immun. 2007 Jul;8(5):387-97. Epub 2007 May 31.
  20. Rioux JD, Xavier RJ, Taylor KD, Silverberg MS, Goyette P, Huett A, Green T, Kuballa P, Barmada MM, Datta LW, Shugart YY, Griffiths AM, Targan SR, Ippoliti AF, Bernard EJ, Mei L, Nicolae DL, Regueiro M, Schumm LP, Steinhart AH, Rotter JI, Duerr RH, Cho JH, Daly MJ, Brant SR. Genome-wide association study identifies new susceptibility loci for Crohn disease and implicates autophagy in disease pathogenesis. Nat Genet. 2007 May;39(5):596-604. Epub 2007 Apr 15.
  21. Dassopoulos T, Nguyen GC, Bitton A, Bromfield GP, Schumm LP, Wu Y, Elkadri A, Regueiro M, Siemanowski B, Torres EA, Gregory FJ, Kane SV, Harrell LE, Franchimont D, Achkar JP, Griffiths A, Brant SR, Rioux JD, Taylor KD, Duerr RH, Silverberg MS, Cho JH, Steinhart AH. Assessment of reliability and validity of IBD phenotyping within the National Institutes of Diabetes and Digestive and Kidney Diseases (NIDDK) IBD Genetics Consortium (IBDGC). Inflamm Bowel Dis. 2007 Aug;13(8):975-83.
  22. Lal S, Appelton J, Mascarenhas J, Stempak JM, Esplen MJ, Silverberg MS. Attitudes toward genetic testing in patients with inflammatory bowel disease. Eur J Gastroenterol Hepatol. 2007 Apr;19(4):321-7.
  23. Hugot JP, Zaccaria I, Cavanaugh J, Yang H, Vermeire S, Lappalainen M, Schreiber S, Annese V, Jewell DP, Fowler EV, Brant SR, Silverberg MS, Cho J, Rioux JD, Satsangi J, Parkes M; for the IBD International Genetics Consortium. Prevalence of CARD15/NOD2 mutations in Caucasian healthy people. Am J Gastroenterol. 2007 Jun;102(6):1259-67. Epub 2007 Feb 23.
  24. Silverberg MS, Duerr RH, Brant SR, Bromfield G, Datta LW, Jani N, Kane SV, Rotter JI, Philip Schumm L, Hillary Steinhart A, Taylor KD, Yang H, Cho JH, Rioux JD, Daly MJ; NIDDK IBD Genetics Consortium. Refined genomic localization and ethnic differences observed for the IBD5 association with Crohn's disease. Eur J Hum Genet. 2007 Mar;15(3):328-35. Epub 2007 Jan 10.
  25. van Bodegraven AA, Curley CR, Hunt KA, Monsuur AJ, Linskens RK, Onnie CM, Crusius JB, Annese V, Latiano A, Silverberg MS, Bitton A, Fisher SA, Steinhart AH, Forbes A, Sanderson J, Prescott NJ, Strachan DP, Playford RJ, Mathew CG, Wijmenga C, Daly MJ, Rioux JD, van Heel DA. Genetic variation in myosin IXB is associated with ulcerative colitis. Gastroenterology. 2006 Dec;131(6):1768-74. Epub 2006 Sep 8.
  26. Duerr RH, Taylor KD, Brant SR, Rioux JD, Silverberg MS, Daly MJ, Steinhart AH, Abraham C, Regueiro M, Griffiths A, Dassopoulos T, Bitton A, Yang H, Targan S, Datta LW, Kistner EO, Schumm LP, Lee AT, Gregersen PK, Barmada MM, Rotter JI, Nicolae DL, Cho JH. A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science. 2006 Dec 1;314(5804):1461-3. Epub 2006 Oct 26.
  27. Lal S, Stempak JM, Law C, Elkadri AA, Steinhart AH, Silverberg MS. Association between the C3435T polymorphism of the MDR1 gene and Crohn's disease. Inflamm Bowel Dis. 2006 Oct;12(10):1006-7. No abstract available.
  28. Nguyen GC, Torres EA, Regueiro M, Bromfield G, Bitton A, Stempak J, Dassopoulos T, Schumm P, Gregory FJ, Griffiths AM, Hanauer SB, Hanson J, Harris ML, Kane SV, Orkwis HK, Lahaie R, Oliva-Hemker M, Pare P, Wild GE, Rioux JD, Yang H, Duerr RH, Cho JH, Steinhart AH, Brant SR, Silverberg MS. Inflammatory bowel disease characteristics among African Americans, Hispanics, and non-Hispanic Whites: characterization of a large North American cohort. Am J Gastroenterol. 2006 May;101(5):1012-23.
  29. Achkar JP, Dassopoulos T, Silverberg MS, Tuvlin JA, Duerr RH, Brant SR, Siminovitch K, Reddy D, Datta LW, Bayless TM, Zhang L, Barmada MM, Rioux JD, Steinhart AH, McLeod RS, Griffiths AM, Cohen Z, Yang H, Bromfield GP, Schumm P, Hanauer SB, Cho JH, Nicolae DL. Phenotype-stratified genetic linkage study demonstrates that IBD2 is an extensive ulcerative colitis locus. Am J Gastroenterol. 2006 Mar;101(3):572-80.


Entrez PubMed (a database of research articles): You can type in keywords (e.g. genetics and Inflammatory Bowel Disease) and generate a list of research articles in this area.

Dr. Mark Silverberg's Publications: This link lists research articles Dr. Silverberg has published.

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