Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47.
Anderson CA., Boucher G., Lees CW., Franke A., D'Amato M., Taylor KD., Lee JC., Goyette P., Imielinski M., Latiano A., Lagacé C., Scott R., Amininejad L., Bumpstead S., Baidoo L., Baldassano RN., Barclay M., Bayless TM., Brand S., Büning C., Colombel J-F., Denson LA., De Vos M., Dubinsky M., Edwards C., Ellinghaus D., Fehrmann RSN., Floyd JAB., Florin T., Franchimont D., Franke L., Georges M., Glas J., Glazer NL., Guthery SL., Haritunians T., Hayward NK., Hugot J-P., Jobin G., Laukens D., Lawrance I., Lémann M., Levine A., Libioulle C., Louis E., McGovern DP., Milla M., Montgomery GW., Morley KI., Mowat C., Ng A., Newman W., Ophoff RA., Papi L., Palmieri O., Peyrin-Biroulet L., Panés J., Phillips A., Prescott NJ., Proctor DD., Roberts R., Russell R., Rutgeerts P., Sanderson J., Sans M., Schumm P., Seibold F., Sharma Y., Simms LA., Seielstad M., Steinhart AH., Targan SR., van den Berg LH., Vatn M., Verspaget H., Walters T., Wijmenga C., Wilson DC., Westra H-J., Xavier RJ., Zhao ZZ., Ponsioen CY., Andersen V., Torkvist L., Gazouli M., Anagnou NP., Karlsen TH., Kupcinskas L., Sventoraityte J., Mansfield JC., Kugathasan S., Silverberg MS., Halfvarson J., Rotter JI., Mathew CG., Griffiths AM., Gearry R., Ahmad T., Brant SR., Chamaillard M., Satsangi J., Cho JH., Schreiber S., Daly MJ., Barrett JC., Parkes M., Annese V., Hakonarson H., Radford-Smith G., Duerr RH., Vermeire S., Weersma RK., Rioux JD.
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.