BACKGROUND & AIMS: Identifying shared and disease-specific susceptibility loci for Crohn's disease (CD) and ulcerative colitis (UC) would help define the biologic relationship between the inflammatory bowel diseases. More than 30 CD susceptibility loci have been identified. These represent important candidate susceptibility loci for UC. Loci discovered by the index genome scans in CD have previously been tested for association with UC, but those identified in the recent meta-analysis await such investigation. Furthermore, the recently identified UC locus at ECM1 requires formal testing for association with CD. METHODS: We analyzed 45 single nucleotide polymorphisms, tagging 29 of the loci recently associated with CD in 2527 UC cases and 4070 population controls. We also genotyped the UC-associated ECM1 variant rs11205387 in 1560 CD patients and 3028 controls. RESULTS: Nine regions showed association with UC at a threshold corrected for the 29 loci tested (P < .0017). The strongest association (P = 4.13 x 10(-8); odds ratio = 1.27) was identified with a 170-kilobase region on chromosome 1q32 that contains 3 genes. We also found association with JAK2 and replicated a recently reported association with STAT3, further implicating the role of this signaling pathway in inflammatory bowel disease. Additional novel UC susceptibility genes were LYRM4 and CDKAL1. Twenty of the loci were not associated with UC, and several appear to be specific to CD. ECM1 variation was not associated with CD. CONCLUSIONS: Collectively, these data help define the genetic relationship between CD and UC and characterize common, as well as disease-specific mechanisms of pathogenesis.
BACKGROUND & AIMS: Identifying shared and disease-specific susceptibility loci for Crohn's disease (CD) and ulcerative colitis (UC) would help define the biologic relationship between the inflammatory bowel diseases. More than 30 CD susceptibility loci have been identified. These represent important candidate susceptibility loci for UC. Loci discovered by the index genome scans in CD have previously been tested for association with UC, but those identified in the recent meta-analysis await such investigation. Furthermore, the recently identified UC locus at ECM1 requires formal testing for association with CD. METHODS: We analyzed 45 single nucleotide polymorphisms, tagging 29 of the loci recently associated with CD in 2527 UC cases and 4070 population controls. We also genotyped the UC-associated ECM1 variant rs11205387 in 1560 CD patients and 3028 controls. RESULTS: Nine regions showed association with UC at a threshold corrected for the 29 loci tested (P < .0017). The strongest association (P = 4.13 x 10(-8); odds ratio = 1.27) was identified with a 170-kilobase region on chromosome 1q32 that contains 3 genes. We also found association with JAK2 and replicated a recently reported association with STAT3, further implicating the role of this signaling pathway in inflammatory bowel disease. Additional novel UC susceptibility genes were LYRM4 and CDKAL1. Twenty of the loci were not associated with UC, and several appear to be specific to CD. ECM1 variation was not associated with CD. CONCLUSIONS: Collectively, these data help define the genetic relationship between CD and UC and characterize common, as well as disease-specific mechanisms of pathogenesis.
Authors: Andre Franke; Tobias Balschun; Tom H Karlsen; Jürgen Hedderich; Sandra May; Tim Lu; Dörthe Schuldt; Susanna Nikolaus; Philip Rosenstiel; Michael Krawczak; Stefan Schreiber Journal: Nat Genet Date: 2008-04-27 Impact factor: 38.330
Authors: John V Raelson; Randall D Little; Andreas Ruether; Hélène Fournier; Bruno Paquin; Paul Van Eerdewegh; W E C Bradley; Pascal Croteau; Quynh Nguyen-Huu; Jonathan Segal; Sophie Debrus; René Allard; Philip Rosenstiel; Andre Franke; Gunnar Jacobs; Susanna Nikolaus; Jean-Michel Vidal; Peter Szego; Nathalie Laplante; Hilary F Clark; René J Paulussen; John W Hooper; Tim P Keith; Abdelmajid Belouchi; Stefan Schreiber Journal: Proc Natl Acad Sci U S A Date: 2007-09-05 Impact factor: 11.205
Authors: John D Rioux; Ramnik J Xavier; Kent D Taylor; Mark S Silverberg; Philippe Goyette; Alan Huett; Todd Green; Petric Kuballa; M Michael Barmada; Lisa Wu Datta; Yin Yao Shugart; Anne M Griffiths; Stephan R Targan; Andrew F Ippoliti; Edmond-Jean Bernard; Ling Mei; Dan L Nicolae; Miguel Regueiro; L Philip Schumm; A Hillary Steinhart; Jerome I Rotter; Richard H Duerr; Judy H Cho; Mark J Daly; Steven R Brant Journal: Nat Genet Date: 2007-04-15 Impact factor: 38.330
Authors: J P Hugot; M Chamaillard; H Zouali; S Lesage; J P Cézard; J Belaiche; S Almer; C Tysk; C A O'Morain; M Gassull; V Binder; Y Finkel; A Cortot; R Modigliani; P Laurent-Puig; C Gower-Rousseau; J Macry; J F Colombel; M Sahbatou; G Thomas Journal: Nature Date: 2001-05-31 Impact factor: 49.962
Authors: Y Ogura; D K Bonen; N Inohara; D L Nicolae; F F Chen; R Ramos; H Britton; T Moran; R Karaliuskas; R H Duerr; J P Achkar; S R Brant; T M Bayless; B S Kirschner; S B Hanauer; G Nuñez; J H Cho Journal: Nature Date: 2001-05-31 Impact factor: 49.962
Authors: Jochen Hampe; Andre Franke; Philip Rosenstiel; Andreas Till; Markus Teuber; Klaus Huse; Mario Albrecht; Gabriele Mayr; Francisco M De La Vega; Jason Briggs; Simone Günther; Natalie J Prescott; Clive M Onnie; Robert Häsler; Bence Sipos; Ulrich R Fölsch; Thomas Lengauer; Matthias Platzer; Christopher G Mathew; Michael Krawczak; Stefan Schreiber Journal: Nat Genet Date: 2006-12-31 Impact factor: 38.330
Authors: Sheila A Fisher; Mark Tremelling; Carl A Anderson; Rhian Gwilliam; Suzannah Bumpstead; Natalie J Prescott; Elaine R Nimmo; Dunecan Massey; Carlo Berzuini; Christopher Johnson; Jeffrey C Barrett; Fraser R Cummings; Hazel Drummond; Charlie W Lees; Clive M Onnie; Catherine E Hanson; Katarzyna Blaszczyk; Mike Inouye; Philip Ewels; Radhi Ravindrarajah; Andrew Keniry; Sarah Hunt; Martyn Carter; Nick Watkins; Willem Ouwehand; Cathryn M Lewis; Lon Cardon; Alan Lobo; Alastair Forbes; Jeremy Sanderson; Derek P Jewell; John C Mansfield; Panos Deloukas; Christopher G Mathew; Miles Parkes; Jack Satsangi Journal: Nat Genet Date: 2008-04-27 Impact factor: 38.330
Authors: Andre Franke; Jochen Hampe; Philip Rosenstiel; Christian Becker; Florian Wagner; Robert Häsler; Randall D Little; Klaus Huse; Andreas Ruether; Tobias Balschun; Michael Wittig; Abdou Elsharawy; Gabriele Mayr; Mario Albrecht; Natalie J Prescott; Clive M Onnie; Hélène Fournier; Tim Keith; Uwe Radelof; Matthias Platzer; Christopher G Mathew; Monika Stoll; Michael Krawczak; Peter Nürnberg; Stefan Schreiber Journal: PLoS One Date: 2007-08-08 Impact factor: 3.240
Authors: Sharon A Chung; Gang Xie; Delnaz Roshandel; Richard Sherva; Jeffrey C Edberg; Megan Kravitz; Paul F Dellaripa; Gary S Hoffman; Alfred D Mahr; Philip Seo; Ulrich Specks; Robert F Spiera; E William St Clair; John H Stone; Robert M Plenge; Katherine A Siminovitch; Peter A Merkel; Paul A Monach Journal: Arthritis Rheum Date: 2012-10
Authors: Thaddeus S Stappenbeck; John D Rioux; Atsushi Mizoguchi; Tatsuya Saitoh; Alan Huett; Arlette Darfeuille-Michaud; Tom Wileman; Noboru Mizushima; Simon Carding; Shizuo Akira; Miles Parkes; Ramnik J Xavier Journal: Autophagy Date: 2011-04-01 Impact factor: 16.016
Authors: Matti Waterman; Wei Xu; Joanne M Stempak; Raquel Milgrom; Charles N Bernstein; Anne M Griffiths; Gordon R Greenberg; A Hillary Steinhart; Mark S Silverberg Journal: Inflamm Bowel Dis Date: 2010-12-10 Impact factor: 5.325
Authors: Joseph Merregaert; Johanna Van Langen; Uwe Hansen; Peter Ponsaerts; Abdoelwaheb El Ghalbzouri; Ellen Steenackers; Xaveer Van Ostade; Sandy Sercu Journal: J Biol Chem Date: 2010-09-24 Impact factor: 5.157
Authors: Marla C Dubinsky; Ling Mei; Madison Friedman; Tanvi Dhere; Talin Haritunians; Hakon Hakonarson; Cecilia Kim; Joseph Glessner; Stephan R Targan; Dermot P McGovern; Kent D Taylor; Jerome I Rotter Journal: Inflamm Bowel Dis Date: 2010-08 Impact factor: 5.325