Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47

Carl A. Anderson, Gabrielle Boucher, Charlie W. Lees, Andre Franke, Mauro D'Amato, Kent D. Taylor, James C. Lee, Philippe Goyette, Marcin Imielinski, Anna Latiano, Caroline Lagacé, Regan Scott, Leila Amininejad, Suzannah Bumpstead, Leonard Baidoo, Robert N. Baldassano, Murray Barclay, Theodore M. Bayless, Stephan Brand, Carsten BüningJean Frédéric Colombel, Lee A. Denson, Martine De Vos, Marla Dubinsky, Cathryn Edwards, David Ellinghaus, Rudolf S.N. Fehrmann, James A.B. Floyd, Timothy Florin, Denis Franchimont, Lude Franke, Michel Georges, Jürgen Glas, Nicole L. Glazer, Stephen L. Guthery, Talin Haritunians, Nicholas K. Hayward, Jean Pierre Hugot, Gilles Jobin, Debby Laukens, Ian Lawrance, Marc Lémann, Arie Levine, Cecile Libioulle, Edouard Louis, Dermot P. McGovern, Monica Milla, Grant W. Montgomery, Katherine I. Morley, Craig Mowat, Aylwin Ng, William Newman, Roel A. Ophoff, Laura Papi, Orazio Palmieri, Laurent Peyrin-Biroulet, Julián Panés, Anne Phillips, Natalie J. Prescott, Deborah D. Proctor, Rebecca Roberts, Richard Russell, Paul Rutgeerts, Jeremy Sanderson, Miquel Sans, Philip Schumm, Frank Seibold, Yashoda Sharma, Lisa A. Simms, Mark Seielstad, A. Hillary Steinhart, Stephan R. Targan, Leonard H. Van Den Berg, Morten Vatn, Hein Verspaget, Thomas Walters, Cisca Wijmenga, David C. Wilson, Harm Jan Westra, Ramnik J. Xavier, Zhen Z. Zhao, Cyriel Y. Ponsioen, Vibeke Andersen, Leif Torkvist, Maria Gazouli, Nicholas P. Anagnou, Tom H. Karlsen, Limas Kupcinskas, Jurgita Sventoraityte, John C. Mansfield, Subra Kugathasan, Mark S. Silverberg, Jonas Halfvarson, Jerome I. Rotter, Christopher G. Mathew, Anne M. Griffiths, Richard Gearry, Tariq Ahmad, Steven R. Brant, Mathias Chamaillard, Jack Satsangi, Judy H. Cho, Stefan Schreiber, Mark J. Daly, Jeffrey C. Barrett, Miles Parkes, Vito Annese, Hakon Hakonarson, Graham Radford-Smith, Richard H. Duerr, Séverine Vermeire, Rinse K. Weersma, John D. Rioux

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915 Citations (Scopus)

Abstract

Genome-wide association studies and candidate gene studies in ulcerative colitis have identified 18 susceptibility loci. We conducted a meta-analysis of six ulcerative colitis genome-wide association study datasets, comprising 6,687 cases and 19,718 controls, and followed up the top association signals in 9,628 cases and 12,917 controls. We identified 29 additional risk loci (P < 5 × 10-8), increasing the number of ulcerative colitis-associated loci to 47. After annotating associated regions using GRAIL, expression quantitative trait loci data and correlations with non-synonymous SNPs, we identified many candidate genes that provide potentially important insights into disease pathogenesis, including IL1R2, IL8RA-IL8RB, IL7R, IL12B, DAP, PRDM1, JAK2, IRF5, GNA12 and LSP1. The total number of confirmed inflammatory bowel disease risk loci is now 99, including a minimum of 28 shared association signals between Crohn's disease and ulcerative colitis.

Original languageEnglish
Pages (from-to)246-252
Number of pages7
JournalNature Genetics
Volume43
Issue number3
DOIs
Publication statusPublished - 1 Jan 2011
Externally publishedYes

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