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Nature genetics, MARCH 2011, VOLUME 43, NUMBER 3

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 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, Julian 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

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 genomewide 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 Å~ 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.

LIST OF PARTICIPANTS

Legend:       Coordinating PI     Participants

1. BE-SMART | 2. CEDAR-UC | 3. COMBINED THERAPY OF BIOLOGICALS AND NEW ORAL DRUGS. | 4. DETECT | 5. DNA BANKING | 6. GENGISCAN | 7. HELP-AID | 8. I-CARE | 9. IMMUNIZATION | 10. LOVE | 11. PACIFIC | 12. PEDIATRIC | 13. SPARE
1 2 3 4 5 6 7 8 9 10 11 12 13
Karen Van Hoeve
- - x x x x
Leila Amininejad x x x
Saskia Appelmans
Filip Baert x x x x x x
Thomas Billiet
Patrick Bontems
Peter Bossuyt x x x x x x
Isabelle Bueres
Katrien Bulté
Guillaume Burnet
Peter Burvenich
Philippe Caenepeel
Olivier Cajot
Christophe Claessens x
Jean-Charles Coche
Jean-Louis Coenegrachts
Arnaud Colard x
Filip Couturier
Lara Crapé
Anneline Cremer x x
Cléo Croonen
Francois D'Heygere x
Steven De Coninck
Elisabeth De Greef x
Marc De Maeyer
Marc De Reuck
Elodie De Ruyck
Nicolas de Suray
Martine De Vos x x x x
Benedicte De Vroey
Stefan Delen
Marie-Armelle Denis
Pieter Dewint x x
Olivier Dewit x x x
Sophie Dewit x x
Joris Dutre
Monica Engelen
Marc Etienne
Marc Ferrante x x x x x
René Fiasse
Fernand Fontaine x x
Denis Franchimont x x x x x x
Silke François
Jeroen Geldof
Bruno Hauser
Pieter Hindryckx x
Ilse Hoffman
Tom Holvoet
Alice Hoyois
Evelien Humblet x
Saskia Ilegems
Aranzazu Jauregui Amezaga
Guy Lambrecht x x x
Pierre Lammens
Claire Liefferinckx x
Triana Lobaton
Edouard Louis x x x x x
Elisabeth Macken x
Marie-Christine Mairlot
Jean-Marc Maisin
Fazia Mana x
Walter Margos
Fady Mokaddem
Kim Moubax
Vinciane Muls
Carmen Musala
Michele Ngassa
Maja Noman
Hanne Ooms
An Outtier
Romy Ouziel
Harald Peeters
Annelies Posen
Philippe Potvin
Lieven Pouillon
Jean-Francois Rahier x x x x x x
Catherine Reenaers x x x
João Sabino
Caroline Saudoyer
Michael Schapira
Nathalie Schoofs
Nele Schoofs
Alexandra Sermeus
Francoise Smets
Michaël Somers
Dirk Staessen
Marjan Steppe
Beatrijs Strubbe x
Jo Swinnen
Clara Thienpont
Marie Truyens
Haydeh Vafa
Gert Van Assche
Stephanie Van Biervliet
Frank Van De Mierop
Gaëtan Van Den Steen
Jurgen Van Dongen
Evi Van Dyck
Andre Van Gossum
Philippe Van Hootegem x x
Catherine Van Kemseke
Wouter Van Moerkercke x x x
Steven Van Outryve
Stijn Vanden Branden x x x x
Liv Vandermeulen
Jo Vandervoort
Gigi Veereman x
Severine Vermeire x x x
Annelies Verreth
Bram Verstockt
Francis Weyn
Barbara Willandt