Common variants at five new loci associated with early-onset inflammatory bowel disease.

Marcin Imielinski; Robert N Baldassano; Anne Griffiths; Richard K Russell; Vito Annese; Marla Dubinsky; Subra Kugathasan; Jonathan P Bradfield; Thomas D Walters; Patrick Sleiman; +108 more... Cecilia E Kim; Aleixo Muise; Kai Wang; Joseph T Glessner; Shehzad Saeed; Haitao Zhang; Edward C Frackelton; Cuiping Hou; James H Flory; George Otieno; Rosetta M Chiavacci; Robert Grundmeier; Massimo Castro; Anna Latiano; Bruno Dallapiccola; Joanne Stempak; Debra J Abrams; Kent Taylor; Dermot McGovern; Western Regional Alliance for Pediatric IBD; Gary Silber; Iwona Wrobel; Antonio Quiros; International IBD Genetics Consortium; Jeffrey C Barrett; Sarah Hansoul; Dan L Nicolae; Judy H Cho; Richard H Duerr; John D Rioux; Steven R Brant; Mark S Silverberg; Kent D Taylor; M Michael Barmuda; Alain Bitton; Themistocles Dassopoulos; Lisa Wu Datta; Todd Green; Anne M Griffiths; Emily O Kistner; Michael T Murtha; Miguel D Regueiro; Jerome I Rotter; L Philip Schumm; A Hillary Steinhart; Stephen R Targan; Ramnik J Xavier; NIDDK IBD Genetics Consortium; Cécile Libioulle; Cynthia Sandor; Mark Lathrop; Jacques Belaiche; Olivier Dewit; Ivo Gut; Simon Heath; Debby Laukens; Myriam Mni; Paul Rutgeerts; André Van Gossum; Diana Zelenika; Denis Franchimont; JP Hugot; Martine de Vos; Severine Vermeire; Edouard Louis; Belgian-French IBD Consortium; Wellcome Trust Case Control Consortium; Lon R Cardon; Carl A Anderson; Hazel Drummond; Elaine Nimmo; Tariq Ahmad; Natalie J Prescott; Clive M Onnie; Sheila A Fisher; Jonathan Marchini; Jilur Ghori; Suzannah Bumpstead; Rhian Gwillam; Mark Tremelling; Panos Delukas; John Mansfield; Derek Jewell; Jack Satsangi; Christopher G Mathew; Miles Parkes; Michel Georges; Mark J Daly; Melvin B Heyman; George D Ferry; Barbara Kirschner; Jessica Lee; Jonah Essers; Richard Grand; Michael Stephens; Arie Levine; David Piccoli; John Van Limbergen; Salvatore Cucchiara; Dimitri S Monos; Stephen L Guthery; Lee Denson; David C Wilson; Straun FA Grant; Mark Daly; Mark S Silverberg; Jack Satsangi; Hakon Hakonarson; (2009) Common variants at five new loci associated with early-onset inflammatory bowel disease. Nat Genet, 41 (12). pp. 1335-1340. ISSN 1061-4036 DOI: 10.1038/ng.489
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The inflammatory bowel diseases (IBD) Crohn's disease and ulcerative colitis are common causes of morbidity in children and young adults in the western world. Here we report the results of a genome-wide association study in early-onset IBD involving 3,426 affected individuals and 11,963 genetically matched controls recruited through international collaborations in Europe and North America, thereby extending the results from a previous study of 1,011 individuals with early-onset IBD. We have identified five new regions associated with early-onset IBD susceptibility, including 16p11 near the cytokine gene IL27 (rs8049439, P = 2.41 x 10(-9)), 22q12 (rs2412973, P = 1.55 x 10(-9)), 10q22 (rs1250550, P = 5.63 x 10(-9)), 2q37 (rs4676410, P = 3.64 x 10(-8)) and 19q13.11 (rs10500264, P = 4.26 x 10(-10)). Our scan also detected associations at 23 of 32 loci previously implicated in adult-onset Crohn's disease and at 8 of 17 loci implicated in adult-onset ulcerative colitis, highlighting the close pathogenetic relationship between early- and adult-onset IBD.

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