Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci

Franke, A.; McGovern, D.P.B.; Barrett, J.C.; Wang, K.; Radford-Smith, G.L.; Ahmad, T.; ... ; Parkes, M. (2010)

Article / Letter to editor

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 x 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.

• inflammatory-bowel-disease sequence variants common variants nedd4 family association gene identification receptor protein activation

• All authors: Franke, A.; McGovern, D.P.B.; Barrett, J.C.; Wang, K.; Radford-Smith, G.L.; Ahmad, T.; Lees, C.W.; Balschun, T.; Lee, J.; Roberts, R.; Anderson, C.A.; Bis, J.C.; Bumpstead, S.; Ellinghaus, D.; Festen, E.M.; Georges, M.; Green, T.; Haritunians, T.; Jostins, L.; Latiano, A.; Mathew, C.G.; Montgomery, G.W.; Prescott, N.J.; Raychaudhuri, S.; Rotter, J.I.; Schumm, P.; Sharma, Y.; Simms, L.A.; Taylor, K.D.; Whiteman, D.; Wijmenga, C.; Baldassano, R.N.; Barclay, M.; Bayless, T.M.; Brand, S.; Buning, C.; Cohen, A.; Colombel, J.F.; Cottone, M.; Stronati, L.; Denson, T.; Vos, M. de; D'Inca, R.; Dubinsky, M.; Edwards, C.; Florin, T.; Franchimont, D.; Gearry, R.; Glas, J.; Gossum, A. van; Guthery, S.L.; Halfvarson, J.; Verspaget, H.W.; Hugot, J.P.; Karban, A.; Laukens, D.; Lawrance, I.; Lemann, M.; Levine, A.; Libioulle, C.; Louis, E.; Mowat, C.; Newman, W.; Panes, J.; Phillips, A.; Proctor, D.D.; Regueiro, M.; Russell, R.; Rutgeerts, P.; Sanderson, J.; Sans, M.; Seibold, F.; Steinhart, A.H.; Stokkers, P.C.F.; Torkvist, L.; Kullak-Ublick, G.; Wilson, D.; Walters, T.; Targan, S.R.; Brant, S.R.; Rioux, J.D.; D'Amato, M.; Weersma, R.K.; Kugathasan, S.; Griffiths, A.M.; Mansfield, J.C.; Vermeire, S.; Duerr, R.H.; Silverberg, M.S.; Satsangi, J.; Schreiber, S.; Cho, J.H.; Annese, V.; Hakonarson, H.; Daly, M.J.; Parkes, M.
• Date: 2010-12-31
• Journal: Nature Genetics
• Volume: 42
• Issue: 12
• Pages: 1118
• DOI: doi:10.1038/ng.717