Title | Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. |
Publication Type | Journal Article |
Year of Publication | 2010 |
Authors | 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, A Steinhart, H, Stokkers, PCF, Törkvist, 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 |
Journal | Nat Genet |
Volume | 42 |
Issue | 12 |
Pagination | 1118-25 |
Date Published | 2010 Dec |
ISSN | 1546-1718 |
Keywords | Computational Biology, Crohn Disease, Genetic Linkage, Genetic Loci, Genetic Predisposition to Disease, Genetic Variation, Genome, Human, Genome-Wide Association Study, Humans, Reproducibility of Results |
Abstract | <p>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.</p> |
DOI | 10.1038/ng.717 |
Alternate Journal | Nat. Genet. |
PubMed ID | 21102463 |
PubMed Central ID | PMC3299551 |
Grant List | M01-RR00425 / RR / NCRR NIH HHS / United States K08 AR055688-03 / AR / NIAMS NIH HHS / United States K23 DK069513 / DK / NIDDK NIH HHS / United States WT089120/Z/09/Z / / Wellcome Trust / United Kingdom DK062422 / DK / NIDDK NIH HHS / United States U01 DK062413 / DK / NIDDK NIH HHS / United States DK069513 / DK / NIDDK NIH HHS / United States N01-HC-85085 / HC / NHLBI NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States P30 DK043351 / DK / NIDDK NIH HHS / United States N01-HC-85081 / HC / NHLBI NIH HHS / United States R21 DK084554 / DK / NIDDK NIH HHS / United States DK064869 / DK / NIDDK NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States DK062423 / DK / NIDDK NIH HHS / United States / / Medical Research Council / United Kingdom U01 DK062432 / DK / NIDDK NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States R01 DK064869 / DK / NIDDK NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States U01 DK062429 / DK / NIDDK NIH HHS / United States N01-HC-85082 / HC / NHLBI NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States K08 AR055688-01A1S1 / AR / NIAMS NIH HHS / United States N01 HC-55222 / HC / NHLBI NIH HHS / United States U01 DK062422 / DK / NIDDK NIH HHS / United States G0800759 / / Medical Research Council / United Kingdom N01-HC-85083 / HC / NHLBI NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States N01-HC-85080 / HC / NHLBI NIH HHS / United States CZB/4/540 / / Chief Scientist Office / United Kingdom DK062431 / DK / NIDDK NIH HHS / United States M01 RR000425 / RR / NCRR NIH HHS / United States DK062420 / DK / NIDDK NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States R03 DK076984 / DK / NIDDK NIH HHS / United States 089120 / / Wellcome Trust / United Kingdom DK 063491 / DK / NIDDK NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States U01 DK062423 / DK / NIDDK NIH HHS / United States K08 AR055688-04 / AR / NIAMS NIH HHS / United States DK062429 / DK / NIDDK NIH HHS / United States P01-DK046763 / DK / NIDDK NIH HHS / United States K08 AR055688 / AR / NIAMS NIH HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States P01 DK046763 / DK / NIDDK NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States G0800675 / / Medical Research Council / United Kingdom N01 HC035129 / HC / NHLBI NIH HHS / United States DK062432 / DK / NIDDK NIH HHS / United States N01-HC-85084 / HC / NHLBI NIH HHS / United States DK062413 / DK / NIDDK NIH HHS / United States U01 DK062420 / DK / NIDDK NIH HHS / United States U01 DK062431 / DK / NIDDK NIH HHS / United States G0600329 / / Medical Research Council / United Kingdom DK084554 / DK / NIDDK NIH HHS / United States DK76984 / DK / NIDDK NIH HHS / United States |