Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci

Publication

Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci

Journal Paper/Review - Dec 1, 2010

Glas Jürgen, Mowat Craig, Newman William, Panés Julián, Phillips Anne, Proctor Deborah D, Regueiro Miguel, Russell Richard, Rutgeerts Paul, Sanderson Jeremy, Sans Miquel, Louis Edouard, Libioulle Cecile, Van Gossum Andre, Guthery Stephen L, Halfvarson Jonas, Verspaget Hein W, Hugot Jean-Pierre, Karban Amir, Laukens Debby, Lawrance Ian, Lemann Marc, Levine Arie, Seibold Frank, Steinhart A Hillary, Mansfield John C, Vermeire Severine, Duerr Richard H, Silverberg Mark S, Satsangi Jack, Schreiber Stefan, Cho Judy H, Annese Vito, Hakonarson Hakon, Daly Mark J, Griffiths Anne M, Kugathasan Subra, Stokkers Pieter C F, Torkvist Leif, Kullak-Ublick Gerd, Wilson David, Walters Thomas, Targan Stephan R, Brant Steven R, Rioux John D, D'Amato Mauro, Weersma Rinse K, Parkes Miles, Franke Andre, Ellinghaus David, Festen Eleonora M, Georges Michel, Green Todd, Haritunians Talin, Jostins Luke, Latiano Anna, Mathew Christopher G, Montgomery Grant W, Prescott Natalie J, Bumpstead Suzanne, Bis Joshua C, McGovern Dermot P B, Barrett Jeffrey C, Wang Kai, Radford-Smith Graham L, Ahmad Tariq, Lees Charlie W, Balschun Tobias, Lee James, Roberts Rebecca, Anderson Carl A, Raychaudhuri Soumya, Rotter Jerome I, Colombel Jean-Frederick, Cottone Mario, Stronati Laura, Denson Ted, De Vos Martine, D'Inca Renata, Dubinsky Marla, Edwards Cathryn, Florin Tim, Franchimont Denis, Cohen Albert, Büning Carsten, Schumm Philip, Sharma Yashoda, Simms Lisa A, Taylor Kent D, Whiteman David, Wijmenga Cisca, Baldassano Robert N, Barclay Murray, Bayless Theodore M, Brand Stephan, Gearry Richard

Citation

Glas J, Mowat C, Newman W, Panés J, Phillips A, Proctor D, Regueiro M, Russell R, Rutgeerts P, Sanderson J, Sans M, Louis E, Libioulle C, Van Gossum A, Guthery S, Halfvarson J, Verspaget H, Hugot J, Karban A, Laukens D, Lawrance I, Lemann M, Levine A, Seibold F, Steinhart A, Mansfield J, Vermeire S, Duerr R, Silverberg M, Satsangi J, Schreiber S, Cho J, Annese V, Hakonarson H, Daly M, Griffiths A, Kugathasan S, Stokkers P, Torkvist L, Kullak-Ublick G, Wilson D, Walters T, Targan S, Brant S, Rioux J, D'Amato M, Weersma R, Parkes M, Franke A, Ellinghaus D, Festen E, Georges M, Green T, Haritunians T, Jostins L, Latiano A, Mathew C, Montgomery G, Prescott N, Bumpstead S, Bis J, McGovern D, Barrett J, Wang K, Radford-Smith G, Ahmad T, Lees C, Balschun T, Lee J, Roberts R, Anderson C, Raychaudhuri S, Rotter J, Colombel J, Cottone M, Stronati L, Denson T, De Vos M, D'Inca R, Dubinsky M, Edwards C, Florin T, Franchimont D, Cohen A, Büning C, Schumm P, Sharma Y, Simms L, Taylor K, Whiteman D, Wijmenga C, Baldassano R, Barclay M, Bayless T, Brand S, Gearry R. Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. Nat Genet 2010; 42:1118-25.

Type

Journal Paper/Review (English)

Journal

Nat Genet 2010; 42

Publication Date

Dec 1, 2010

Issn Electronic

1546-1718

Pages

1118-25

Brief description/objective

We undertook a meta-analysis of six Crohn's disease genome-wide association studies (GWAS) comprising 6,333 affected individuals (cases) and 15,056 controls and followed up the top association signals in 15,694 cases, 14,026 controls and 414 parent-offspring trios. We identified 30 new susceptibility loci meeting genome-wide significance (P < 5 × 10⁻⁸). A series of in silico analyses highlighted particular genes within these loci and, together with manual curation, implicated functionally interesting candidate genes including SMAD3, ERAP2, IL10, IL2RA, TYK2, FUT2, DNMT3A, DENND1B, BACH2 and TAGAP. Combined with previously confirmed loci, these results identify 71 distinct loci with genome-wide significant evidence for association with Crohn's disease.