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

2009; Nature Portfolio; Volume: 41; Issue: 12 Linguagem: Inglês

10.1038/ng.489

1546-1718

Marcin Imieliński, Robert N. Baldassano, Anne M. Griffiths, Richard K. Russell, Vito Annese, Marla Dubinsky, Subra Kugathasan, Jonathan P. Bradfield, Thomas D. Walters, Patrick Sleiman, Cecilia E Kim, Aleixo M. Muise, Kai Wang, Joseph Glessner, Shehzad A. Saeed, Haitao Zhang, Edward C. Frackelton, Cuiping Hou, James H. Flory, George Otieno, Rosetta Chiavacci, Robert W. Grundmeier, Massimo Castro, Anna Latiano, Bruno Dallapiccola, Joanne M. Stempak, Debra Abrams, Kent D. Taylor, Dermot McGovern, Melvin B. Heyman, George D. Ferry, Barbara S. Kirschner, Jessica Lee, Jonah Essers, Richard J. Grand, Michael C. Stephens, Arie Levine, David A. Piccoli, Johan Van Limbergen, Salvatore Cucchiara, Dimitri Monos, Stephen L. Guthery, Lee A. Denson, David C. Wilson, Struan F.A. Grant, Mark J. Daly, Mark S. Silverberg, Jack Satsangi, Hákon Hákonarson,

Autoimmune and Inflammatory Disorders Research

Hakon Hakonarson and colleagues report the discovery of five new regions associated with susceptibility to early-onset inflammatory bowel disease. They also identify multiple loci previously implicated in the etiology of adult-onset Crohn's disease and/or ulcerative colitis as risk factors for early-onset forms of these diseases. 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 IBD1. We have identified five new regions associated with early-onset IBD susceptibility, including 16p11 near the cytokine gene IL27 (rs8049439, P = 2.41 × 10−9), 22q12 (rs2412973, P = 1.55 × 10−9), 10q22 (rs1250550, P = 5.63 × 10−9), 2q37 (rs4676410, P = 3.64 × 10−8) and 19q13.11 (rs10500264, P = 4.26 × 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.