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. © 2011 Nature America, Inc. All rights reserved.
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.; 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.; De Vos, M.; 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.; Van Den Berg, L. H.; 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.. - In: NATURE GENETICS. - ISSN 1061-4036. - 43:3(2011), pp. 246-252. [10.1038/ng.764]
Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47
Annese V.;
2011-01-01
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. © 2011 Nature America, Inc. All rights reserved.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
