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

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

Published Web Location

https://doi.org/10.1038/ng.764
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.

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