Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci.
Franke A., McGovern DPB., Barrett JC., Wang K., Radford-Smith GL., Ahmad T., Lees CW., Balschun T., Lee J., Roberts R., Anderson CA., Bis JC., Bumpstead S., Ellinghaus D., Festen EM., Georges M., Green T., Haritunians T., Jostins L., Latiano A., Mathew CG., Montgomery GW., Prescott NJ., Raychaudhuri S., Rotter JI., Schumm P., Sharma Y., Simms LA., Taylor KD., Whiteman D., Wijmenga C., Baldassano RN., Barclay M., Bayless TM., Brand S., Büning C., Cohen A., Colombel J-F., Cottone M., Stronati L., Denson T., De Vos M., D'Inca R., Dubinsky M., Edwards C., Florin T., Franchimont D., Gearry R., Glas J., Van Gossum A., Guthery SL., Halfvarson J., Verspaget HW., Hugot J-P., Karban A., Laukens D., Lawrance I., Lemann M., Levine A., Libioulle C., Louis E., Mowat C., Newman W., Panés J., Phillips A., Proctor DD., Regueiro M., Russell R., Rutgeerts P., Sanderson J., Sans M., Seibold F., Steinhart AH., Stokkers PCF., Torkvist L., Kullak-Ublick G., Wilson D., Walters T., Targan SR., Brant SR., Rioux JD., D'Amato M., Weersma RK., Kugathasan S., Griffiths AM., Mansfield JC., Vermeire S., Duerr RH., Silverberg MS., Satsangi J., Schreiber S., Cho JH., Annese V., Hakonarson H., Daly MJ., Parkes M.
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.