Skip to main content
SpringerLink
Log in

Genetik des Morbus Crohn und der Colitis ulcerosa

Aktueller Stand 15 Jahre nach Entdeckung von NOD2

Genetics of Crohn’s disease and ulcerative colitis

Current status 15 years after discovery of NOD2

  • Gastroenterologie
  • Published:
Wiener klinisches Magazin Aims and scope

Zusammenfassung

Modernste Technologien der genetischen Forschung bieten der Medizin einen ganz neuen Zugangsweg zur Entdeckung von genetischen Krankheitsursachen. Innerhalb der letzten 15 Jahre wurden die genetischen Untersuchungstechniken in einem solchen Umfang weiterentwickelt, dass heute auch die Untersuchung „komplexer“ Erkrankungen und die Entschlüsselung kompletter Patientengenome innerhalb kürzester Zeit möglich sind.

Für die chronisch-entzündlichen Darmerkrankungen (CED) Morbus Crohn und Colitis ulcerosa sind mittlerweile über 200 assoziierte Genloci bekannt. Die Mehrheit der identifizierten Loci überschneidet sich nicht nur zwischen Morbus Crohn und Colitis ulcerosa, was deren klinische Ähnlichkeit widerspiegelt, sondern auch mit anderen chronisch-entzündlichen Erkrankungen, vor allem mit Psoriasis, Morbus Bechterew und primären Immundefizienzen. Die beiden wichtigsten und am besten validierten CED-Krankheitsloci sind nach wie vor NOD2 (für Morbus Crohn) und die HLA-Region (für Colitis ulcerosa). Genetische Analysen in anderen Ethnizitäten (z. B. Asiaten) zeigen nahezu die gleichen assoziierten Risikoloci wie in europäischstämmigen Patienten. Interessanterweise ist NOD2 hier eine Ausnahme.

Die jüngsten großen genetischen Studien bestätigen die Assoziation von Risikovarianten in NOD2 mit Dünndarmbefall bei Morbus Crohn und suggerieren die Existenz von eher drei als zwei Subformen der CED: 1) Colitis ulcerosa, 2) Morbus Crohn mit Dickdarmbefall, 3) Morbus Crohn mit Dünndarmbefall.

Durch hochmoderne Sequenzieranalysen konnten in den letzten Jahren für frühkindliche Formen der CED einzelne Mutationen vor allem in bekannten Immundefizienzgenen (neben den bekannten Mutationen in IL10RA/B), identifiziert und die Erkrankungen damit aufgeklärt werden (monogener Defekt).

Abstract

Modern technologies in genetic research hold the promise of identifying yet unknown causes of diseases, revealing the relevant pathways, and prioritizing therapeutic targets. Technological developments of the last 15 years tremendously contributed to novel genetic findings in complex disease research. Entire patient genomes can now be deciphered within a few days at reasonable and continuously decreasing costs.

More than 200 genetic susceptibility loci have been identified for the inflammatory bowel (IBD) diseases, Crohn’s disease (CD), and ulcerative colitis (UC). Reflecting their clinical similarity, most of the risk loci are shared between CD and UC outside the major histocompatibility complex (MHC). The genetic risk map of IBD is also highly similar to other chronic immune-mediated diseases, especially psoriasis, ankylosing spondylitis, and primary immunedeficiencies. The two best validated IBD disease loci are still NOD2 for CD and the HLA/MHC region on chromosome 6p21 for UC. Genetic investigations in non-European-ancestry cohorts (e. g., from Eastern Asia) also suggest that risk loci are shared across different ancestries. Interestingly, this is not true for NOD2.

A recent large-scale and multicenter study validated the association of susceptibility variants within the NOD2 gene and ileal CD. These genetic analyses also support the theory that rather three than two subtypes of IBD exist: (1) UC, (2) colonic CD, and (3) ileal CD.

Modern high-throughput sequencing studies revealed several monogenic forms of early onset and very early onset IBD, implicating often known immunodeficiency disease loci, including the previously implicated interleukin-10 receptor (IL10RA/B) gene. Thus, identifying a single causative genetic variant in these young patients proves their exact disease cause.

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

Abb. 1
Abb. 2
Abb. 3

Literatur

  1. Anderson CA, Boucher G, Lees CW, Franke A, D’Amato M, Taylor KD, Lee JC, Goyette P, Imielinski M, Latiano A, Lagacé C, Scott R, Amininejad L, Bumpstead S, Baidoo L, Baldassano RN, Barclay M, Bayless TM, Brand S, Büning C, Colombel JF, Denson LA, De Vos M, Dubinsky M, Edwards C, Ellinghaus D, Fehrmann RS, Floyd JA, Florin T, Franchimont D, Franke L, Georges M, Glas J, Glazer NL, Guthery SL, Haritunians T, Hayward NK, Hugot JP, Jobin G, Laukens D, Lawrance I, Lémann M, Levine A, Libioulle C, Louis E, McGovern DP, Milla M, Montgomery GW, Morley KI, Mowat C, Ng A, Newman W, Ophoff RA, Papi L, Palmieri O, Peyrin-Biroulet L, Panés J, Phillips A, Prescott NJ, Proctor DD, Roberts R, Russell R, Rutgeerts P, Sanderson J, Sans M, Schumm P, Seibold F, Sharma Y, Simms LA, Seielstad M, Steinhart AH, Targan SR, van den Berg LH, Vatn M, Verspaget H, Walters T, Wijmenga C, Wilson DC, Westra HJ, Xavier RJ, Zhao ZZ, Ponsioen CY, Andersen V, Torkvist L, Gazouli M, Anagnou NP, Karlsen TH, Kupcinskas L, Sventoraityte J, Mansfield JC, Kugathasan S, Silverberg MS, Halfvarson J, Rotter JI, Mathew CG, Griffiths AM, Gearry R, Ahmad T, Brant SR, Chamaillard M, Satsangi J, Cho JH, Schreiber S, Daly MJ, Barrett JC, Parkes M, Annese V, Hakonarson H, Radford-Smith G, Duerr RH, Vermeire S, Weersma RK, Rioux JD (2011) Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. Nat Genet 43(3):246–252. https://doi.org/10.1038/ng.764

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. 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, Wellcome Trust Case Control Consortium, Belgian-French IBD 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 (2008) Genome-wide association defines more than 30 distinct susceptibility loci for Crohn’s disease. Nat Genet 40(8):955–962. https://doi.org/10.1038/ng.175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Beaudoin M, Goyette P, Boucher G, Lo KS, Rivas MA, Stevens C, Alikashani A, Ladouceur M, Ellinghaus D, Törkvist L, Goel G, Lagacé C, Annese V, Bitton A, Begun J, Brant SR, Bresso F, Cho JH, Duerr RH, Halfvarson J, McGovern DP, Radford-Smith G, Schreiber S, Schumm PL, Sharma Y, Silverberg MS, Weersma RK, Quebec IBD Genetics Consortium, NIDDK IBD Genetics Consortium, International IBD Genetics Consortium, D’Amato M, Vermeire S, Franke A, Lettre G, Xavier RJ, Daly MJ, Rioux JD (2013) Deep resequencing of GWAS loci identifies rare variants in CARD9, IL23R and RNF186 that are associated with ulcerative colitis. PLOS Genet 9(9):e1003723. https://doi.org/10.1371/journal.pgen.1003723

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Brant SR (2011) Update on the heritability of inflammatory bowel disease: the importance of twin studies. Inflamm Bowel Dis 17(1):1–5. https://doi.org/10.1002/ibd.21385

    Article  PubMed  Google Scholar 

  5. Cleynen I, Boucher G, Jostins L, Schumm LP, Zeissig S, Ahmad T, Andersen V, Andrews JM, Annese V, Brand S, Brant SR, Cho JH, Daly MJ, Dubinsky M, Duerr RH, Ferguson LR, Franke A, Gearry RB, Goyette P, Hakonarson H, Halfvarson J, Hov JR, Huang H, Kennedy NA, Kupcinskas L, Lawrance IC, Lee JC, Satsangi J, Schreiber S, Théâtre E, van der Meulen-de Jong AE, Weersma RK, Wilson DC, International Inflammatory Bowel Disease Genetics Consortium, Parkes M, Vermeire S, Rioux JD, Mansfield J, Silverberg MS, Radford-Smith G, McGovern DP, Barrett JC, Lees CW (2016) Inherited determinants of Crohn’s disease and ulcerative colitis phenotypes: a genetic association study. Lancet 387(10014):156–167. https://doi.org/10.1016/S0140-6736(15)00465-1

    Article  PubMed  PubMed Central  Google Scholar 

  6. 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 (2006) A genome-wide association study identifies IL23R as an inflammatory bowel disease gene. Science 314(5804):1461–1463

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Ellinghaus D, Jostins L, Spain SL, Cortes A, Bethune J, Han B, Park YR, Raychaudhuri S, Pouget JG, Hübenthal M, Folseraas T, Wang Y, Esko T, Metspalu A, Westra HJ, Franke L, Pers TH, Weersma RK, Collij V, D’Amato M, Halfvarson J, Jensen AB, Lieb W, Degenhardt F, Forstner AJ, Hofmann A, International IBD Genetics Consortium (IIBDGC), International Genetics of Ankylosing Spondylitis Consortium (IGAS), International PSC Study Group (IPSCSG), Genetic Analysis of Psoriasis Consortium (GAPC), Psoriasis Association Genetics Extension (PAGE), Schreiber S, Mrowietz U, Juran BD, Lazaridis KN, Brunak S, Dale AM, Trembath RC, Weidinger S, Weichenthal M, Ellinghaus E, Elder JT, Barker JN, Andreassen OA, McGovern DP, Karlsen TH, Barrett JC, Parkes M, Brown MA, Franke A (2016) Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease-specific patterns at shared loci. Nat Genet 48(5):510–518. https://doi.org/10.1038/ng.3528

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Farh KK, Marson A, Zhu J, Kleinewietfeld M, Housley WJ, Beik S, Shoresh N, Whitton H, Ryan RJ, Shishkin AA, Hatan M, Carrasco-Alfonso MJ, Mayer D, Luckey CJ, Patsopoulos NA, De Jager PL, Kuchroo VK, Epstein CB, Daly MJ, Hafler DA, Bernstein BE (2015) Genetic and epigenetic fine mapping of causal autoimmune disease variants. Nature 518(7539):337–343. https://doi.org/10.1038/nature13835

    Article  CAS  PubMed  Google Scholar 

  9. Feller M, Huwiler K, Stephan R, Altpeter E, Shang A, Furrer H, Pfyffer GE, Jemmi T, Baumgartner A, Egger M (2007) Mycobacterium avium subspecies paratuberculosis and Crohn’s disease: a systematic review and meta-analysis. Lancet Infect Dis 7(9):607–613

    Article  PubMed  Google Scholar 

  10. Franke A, Balschun T, Karlsen TH, Sventoraityte J, Nikolaus S, Mayr G, Domingues FS, Albrecht M, Nothnagel M, Ellinghaus D, Sina C, Onnie CM, Weersma RK, Stokkers PC, Wijmenga C, Gazouli M, Strachan D, McArdle WL, Vermeire S, Rutgeerts P, Rosenstiel P, Krawczak M, Vatn MH, BSEN study group, Mathew CG, Schreiber S (2008) Sequence variants in IL10, ARPC2 and multiple other loci contribute to ulcerative colitis susceptibility. Nat Genet 40(11):1319–1323. https://doi.org/10.1038/ng.221

    Article  CAS  PubMed  Google Scholar 

  11. 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 (2010) Genome-wide meta-analysis increases to 71 the number of confirmed Crohn’s disease susceptibility loci. Nat Genet 42(12):1118–1125. https://doi.org/10.1038/ng.717

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Goyette P, Boucher G, Mallon D, Ellinghaus E, Jostins L, Huang H, Ripke S, Gusareva ES, Annese V, Hauser SL, Oksenberg JR, Thomsen I, Leslie S, International Inflammatory Bowel Disease Genetics Consortium, Australia and New Zealand IBDGC, Belgium IBD Genetics Consortium, Italian Group for IBD Genetic Consortium, NIDDK Inflammatory Bowel Disease Genetics Consortium, United Kingdom IBDGC, Wellcome Trust Case Control Consortium; Quebec IBD Genetics Consortium, Daly MJ, Van Steen K, Duerr RH, Barrett JC, McGovern DP, Schumm LP, Traherne JA, Carrington MN, Kosmoliaptsis V, Karlsen TH, Franke A, Rioux JD, Quebec IBD Genetics Consortium, Daly MJ, Van Steen K, Duerr RH, Barrett JC, McGovern DP, Schumm LP, Traherne JA, Carrington MN, Kosmoliaptsis V, Karlsen TH, Franke A, Rioux JD (2015) High-density mapping of the MHC identifies a shared role for HLA-DRB1*01:03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis. Nat Genet 47(2):172–179. https://doi.org/10.1038/ng.3176

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Halme L, Paavola-Sakki P, Turunen U, Lappalainen M, Farkkila M, Kontula K (2006) Family and twin studies in inflammatory bowel disease. World J Gastroenterol 12(23):3668–3672

    Article  PubMed  PubMed Central  Google Scholar 

  14. Hampe J, Franke A, Rosenstiel P, Till A, Teuber M, Huse K, Albrecht M, Mayr G, De La Vega FM, Briggs J, Günther S, Prescott NJ, Onnie CM, Häsler R, Sipos B, Fölsch UR, Lengauer T, Platzer M, Mathew CG, Krawczak M, Schreiber S (2007) A genome-wide association scan of nonsynonymous SNPs identifies a susceptibility variant for Crohn disease in ATG16L1. Nat Genet 39(2):207–211

    Article  CAS  PubMed  Google Scholar 

  15. Hugot JP, Laurent-Puig P, Gower-Rousseau C, Olson JM, Lee JC, Beaugerie L, Naom I, Dupas JL, Van Gossum A, Orholm M, Bonaiti-Pellie C, Weissenbach J, Mathew CG, Lennard-Jones JE, Cortot A, Colombel JF, Thomas G (1996) Mapping of a susceptibility locus for Crohn’s disease on chromosome 16. Nature 379(6568):821–823

    Article  CAS  PubMed  Google Scholar 

  16. Hugot JP, Chamaillard M, Zouali H, Lesage S, Cézard JP, Belaiche J, Almer S, Tysk C, O’Morain CA, Gassull M, Binder V, Finkel Y, Cortot A, Modigliani R, Laurent-Puig P, Gower-Rousseau C, Macry J, Colombel JF, Sahbatou M, Thomas G (2001) Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease. Nature 411(6837):599–603

    Article  CAS  PubMed  Google Scholar 

  17. Jostins L, Ripke S, Weersma RK, Duerr RH, McGovern DP, Hui KY, Lee JC, Schumm LP, Sharma Y, Anderson CA, Essers J, Mitrovic M, Ning K, Cleynen I, Theatre E, Spain SL, Raychaudhuri S, Goyette P, Wei Z, Abraham C, Achkar JP, Ahmad T, Amininejad L, Ananthakrishnan AN, Andersen V, Andrews JM, Baidoo L, Balschun T, Bampton PA, Bitton A, Boucher G, Brand S, Büning C, Cohain A, Cichon S, D’Amato M, De Jong D, Devaney KL, Dubinsky M, Edwards C, Ellinghaus D, Ferguson LR, Franchimont D, Fransen K, Gearry R, Georges M, Gieger C, Glas J, Haritunians T, Hart A, Hawkey C, Hedl M, Hu X, Karlsen TH, Kupcinskas L, Kugathasan S, Latiano A, Laukens D, Lawrance IC, Lees CW, Louis E, Mahy G, Mansfield J, Morgan AR, Mowat C, Newman W, Palmieri O, Ponsioen CY, Potocnik U, Prescott NJ, Regueiro M, Rotter JI, Russell RK, Sanderson JD, Sans M, Satsangi J, Schreiber S, Simms LA, Sventoraityte J, Targan SR, Taylor KD, Tremelling M, Verspaget HW, De Vos M, Wijmenga C, Wilson DC, Winkelmann J, Xavier RJ, Zeissig S, Zhang B, Zhang CK, Zhao H, International IBD Genetics Consortium (IIBDGC), Silverberg MS, Annese V, Hakonarson H, Brant SR, Radford-Smith G, Mathew CG, Rioux JD, Schadt EE, Daly MJ, Franke A, Parkes M, Vermeire S, Barrett JC, Cho JH (2012) Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. Nature 491(7422):119–124. https://doi.org/10.1038/nature11582

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Kaplan GG (2015) The global burden of IBD: from 2015 to 2025. Nat Rev Gastroenterol Hepatol 12(12):720–727. https://doi.org/10.1038/nrgastro.2015.150

    Article  PubMed  Google Scholar 

  19. Karlsen TH, Chung BK (2015) Genetic risk and the development of autoimmune liver disease. Dig Dis 33(Suppl 2):13–24. https://doi.org/10.1159/000440706

    Article  PubMed  Google Scholar 

  20. Lees CW, Barrett JC, Parkes M, Satsangi J (2011) New IBD genetics: common pathways with other diseases. Gut 60(12):1739–1753. https://doi.org/10.1136/gut.2009.199679

    Article  CAS  PubMed  Google Scholar 

  21. Liu JZ, van Sommeren S, Huang H, Ng SC, Alberts R, Takahashi A, Ripke S, Lee JC, Jostins L, Shah T, Abedian S, Cheon JH, Cho J, Daryani NE, Franke L, Fuyuno Y, Hart A, Juyal RC, Juyal G, Kim WH, Morris AP, Poustchi H, Newman WG, Midha V, Orchard TR, Vahedi H, Sood A, Sung JJ, Malekzadeh R, Westra HJ, Yamazaki K, Yang SK, International Multiple Sclerosis Genetics Consortium, International IBD Genetics Consortium, Barrett JC, Franke A, Alizadeh BZ, Parkes M, Daly MJ, Kubo M, Anderson CA, Weersma RK (2015) Association analyses identify 38 susceptibility loci for inflammatory bowel disease and highlight shared genetic risk across populations. Nat Genet 47(9):979–986. https://doi.org/10.1038/ng.3359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Mathew CG, Lewis CM (2004) Genetics of inflammatory bowel disease: progress and prospects. Hum Mol Genet 13(1):R161–R168

    Article  CAS  PubMed  Google Scholar 

  23. McGovern DP, Jones MR, Taylor KD, Marciante K, Yan X, Dubinsky M, Ippoliti A, Vasiliauskas E, Berel D, Derkowski C, Dutridge D, Fleshner P, Shih DQ, Melmed G, Mengesha E, King L, Pressman S, Haritunians T, Guo X, Targan SR, Rotter JI, International IBD Genetics Consortium (2010) Fucosyltransferase 2 (FUT2) non-secretor status is associated with Crohn’s disease. Hum Mol Genet 19(17):3468–3476. https://doi.org/10.1093/hmg/ddq248

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Muñoz M, Pong-Wong R, Canela-Xandri O, Rawlik K, Haley CS, Tenesa A (2016) Evaluating the contribution of genetics and familial shared environment to common disease using the UK Biobank. Nat Genet 48(9):980–983. https://doi.org/10.1038/ng.3618

    Article  PubMed  Google Scholar 

  25. Ogura Y, Bonen DK, Inohara N, Nicolae DL, Chen FF, Ramos R, Britton H, Moran T, Karaliuskas R, Duerr RH, Achkar JP, Brant SR, Bayless TM, Kirschner BS, Hanauer SB, Nuñez G, Cho JH (2001) A frameshift mutation in NOD2 associated with susceptibility to Crohn’s disease. Nature 411(6837):603–606

    Article  CAS  PubMed  Google Scholar 

  26. Parkes M, Cortes A, van Heel DA, Brown MA (2013) Genetic insights into common pathways and complex relationships among immune-mediated diseases. Nat Rev Genet 14(9):661–673. https://doi.org/10.1038/nrg3502

    Article  CAS  PubMed  Google Scholar 

  27. Risch N, Merikangas K (1996) The future of genetic studies of complex human diseases. Science 273(5281):1516–1517

    Article  CAS  PubMed  Google Scholar 

  28. 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 PJ, Daly MJ (2011) Deep resequencing of GWAS loci identifies independent rare variants associated with inflammatory bowel disease. Nat Genet 43(11):1066–1073. https://doi.org/10.1038/ng.952

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Tschurtschenthaler M, Kachroo P, Heinsen FA, Adolph TE, Rühlemann MC, Klughammer J, Offner FA, Ammerpohl O, Krueger F, Smallwood S, Szymczak S, Kaser A, Franke A (2016) Paternal chronic colitis causes epigenetic inheritance of susceptibility to colitis. Sci Rep 6:31640. https://doi.org/10.1038/srep31640

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Uhlig HH, Schwerd T, Koletzko S, Shah N, Kammermeier J, Elkadri A, Ouahed J, Wilson DC, Travis SP, Turner D, Klein C, Snapper SB, Muise AM, COLORS in IBD Study Group and NEOPICS (2014) The diagnostic approach to monogenic very early onset inflammatory bowel disease. Gastroenterology 147(5):990–1007.e3. https://doi.org/10.1053/j.gastro.2014.07.023

    Article  PubMed  PubMed Central  Google Scholar 

  31. van Heel DA, Fisher SA, Kirby A, Daly MJ, Rioux JD, Lewis CM, Genome Scan Meta-Analysis Group of the IBD International Genetics Consortium (2004) Inflammatory bowel disease susceptibility loci defined by genome scan meta-analysis of 1952 affected relative pairs. Hum Mol Genet 13(7):763–770

    Article  PubMed  Google Scholar 

  32. Visscher PM, Brown MA, McCarthy MI, Yang J (2012) Five years of GWAS discovery. Am J Hum Genet 90(1):7–24. https://doi.org/10.1016/j.ajhg.2011.11.029

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Wellcome Trust Case Control Consortium (2007) Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447(7145):661–678

    Article  Google Scholar 

  34. Yamazaki K, McGovern D, Ragoussis J, Paolucci M, Butler H, Jewell D, Cardon L, Takazoe M, Tanaka T, Ichimori T, Saito S, Sekine A, Iida A, Takahashi A, Tsunoda T, Lathrop M, Nakamura Y (2005) Single nucleotide polymorphisms in TNFSF15 confer susceptibility to Crohn’s disease. Hum Mol Genet 14(22):3499–3506 (Nov)

    Article  CAS  PubMed  Google Scholar 

  35. Zhang FR, Huang W, Chen SM, Sun LD, Liu H, Li Y, Cui Y, Yan XX, Yang HT, Yang RD, Chu TS, Zhang C, Zhang L, Han JW, Yu GQ, Quan C, Yu YX, Zhang Z, Shi BQ, Zhang LH, Cheng H, Wang CY, Lin Y, Zheng HF, Fu XA, Zuo XB, Wang Q, Long H, Sun YP, Cheng YL, Tian HQ, Zhou FS, Liu HX, Lu WS, He SM, Du WL, Shen M, Jin QY, Wang Y, Low HQ, Erwin T, Yang NH, Li JY, Zhao X, Jiao YL, Mao LG, Yin G, Jiang ZX, Wang XD, Yu JP, Hu ZH, Gong CH, Liu YQ, Liu RY, Wang DM, Wei D, Liu JX, Cao WK, Cao HZ, Li YP, Yan WG, Wei SY, Wang KJ, Hibberd ML, Yang S, Zhang XJ, Liu JJ (2009) Genomewide association study of leprosy. N Engl J Med 361(27):2609–2618. https://doi.org/10.1056/NEJMoa0903753

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institut für Klinische Molekularbiologie, Christian-Albrechts-Universität zu Kiel, Rosalind-Franklin-Str. 12, 24105, Kiel, Deutschland

    Frauke Degenhardt &  Andre Franke

Authors
  1. Frauke Degenhardt
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Andre Franke
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andre Franke.

Ethics declarations

Interessenkonflikt

F. Degenhardt und A. Franke geben an, dass kein Interessenkonflikt besteht.

Dieser Beitrag beinhaltet keine von den Autoren durchgeführten Studien an Menschen oder Tieren.

Additional information

Dieser Beitrag wurde in der Zeitschrift Der Gastroenterologe 2017 · 12:38–48 erstveröffentlicht. Dort ist der Beitrag als open access Publikation auch kostenlos zugänglich und nutzbar. Zweitpublikation mit freundlicher Genehmigung der Autoren.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Degenhardt, F., Franke, A. Genetik des Morbus Crohn und der Colitis ulcerosa. Wien klin Mag 21, 4–13 (2018). https://doi.org/10.1007/s00740-017-0211-0

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00740-017-0211-0

Schlüsselwörter

Keywords

Search

Navigation