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

Anderson, C.A.; Boucher, G.; Lees, C.W.; Franke, A.; D'Amato, M.; Taylor, K.D.; ... ; Rioux, J.D. (2011)

Article / Letter to editor

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 x 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.

• inflammatory-bowel-disease genome-wide association susceptibility loci crohns-disease common variants gene-expression cells multiple protein enrichment

• All authors: Anderson, C.A.; Boucher, G.; Lees, C.W.; Franke, A.; D'Amato, M.; Taylor, K.D.; Lee, J.C.; Goyette, P.; Imielinski, M.; Latiano, A.; Lagace, C.; Scott, R.; Amininejad, L.; Bumpstead, S.; Baidoo, L.; Baldassano, R.N.; Barclay, M.; Bayless, T.M.; Brand, S.; Buning, C.; Colombel, J.F.; Denson, L.A.; Vos, M. de; Dubinsky, M.; Edwards, C.; Ellinghaus, D.; Fehrmann, R.S.N.; Floyd, J.A.B.; Florin, T.; Franchimont, D.; Franke, L.; Georges, M.; Glas, J.; Glazer, N.L.; Guthery, S.L.; Haritunians, T.; Hayward, N.K.; Hugot, J.P.; Jobin, G.; Laukens, D.; Lawrance, I.; Lemann, M.; Levine, A.; Libioulle, C.; Louis, E.; McGovern, D.P.; Milla, M.; Montgomery, G.W.; Morley, K.I.; Mowat, C.; Ng, A.; Newman, W.; Ophoff, R.A.; Papi, L.; Palmieri, O.; Peyrin-Biroulet, L.; Panes, J.; Phillips, A.; Prescott, N.J.; Proctor, D.D.; Roberts, R.; Russell, R.; Rutgeerts, P.; Sanderson, J.; Sans, M.; Schumm, P.; Seibold, F.; Sharma, Y.; Simms, L.A.; Seielstad, M.; Steinhart, A.H.; Targan, S.R.; Berg, L.H. van den; Vatn, M.; Verspaget, H.; Walters, T.; Wijmenga, C.; Wilson, D.C.; Westra, H.J.; Xavier, R.J.; Zhao, Z.Z.; Ponsioen, C.Y.; Andersen, V.; Torkvist, L.; Gazouli, M.; Anagnou, N.P.; Karlsen, T.H.; Kupcinskas, L.; Sventoraityte, J.; Mansfield, J.C.; Kugathasan, S.; Silverberg, M.S.; Halfvarson, J.; Rotter, J.I.; Mathew, C.G.; Griffiths, A.M.; Gearry, R.; Ahmad, T.; Brant, S.R.; Chamaillard, M.; Satsangi, J.; Cho, J.H.; Schreiber, S.; Daly, M.J.; Barrett, J.C.; Parkes, M.; Annese, V.; Hakonarson, H.; Radford-Smith, G.; Duerr, R.H.; Vermeire, S.; Weersma, R.K.; Rioux, J.D.
• Date: 2011-03-31
• Journal: Nature Genetics
• Volume: 43
• Issue: 3
• Pages: 246
• DOI: doi:10.1038/ng.764