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

Authors:
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 Büning, Jean-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
Year of publication:
2011
Volume:
43
Issue:
3
Issn:
1061-4036
Journal title abbreviated:
NAT GENET
Journal title long:
Nature genetics
Impact factor:
31.616
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.