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Nature. 2012 Nov 1;491(7422):119-24. doi: 10.1038/nature11582.

Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.

Collaborators (347)

Barclay M, Peyrin-Biroulet L, Chamaillard M, Colombel JF, Cottone M, Croft A, D'Incà R, Halfvarson J, Hanigan K, Henderson P, Hugot JP, Karban A, Kennedy NA, Khan MA, Lémann M, Levine A, Massey D, Milla M, Montgomery GW, Ng SM, Oikonomou I, Peeters H, Proctor DD, Rahier JF, Roberts R, Rutgeerts P, Seibold F, Stronati L, Taylor KM, Törkvist L, Ublick K, Van Limbergen J, Van Gossum A, Vatn MH, Zhang H, Zhang W, Andrews JM, Bampton PA, Barclay M, Florin TH, Gearry R, Krishnaprasad K, Lawrance IC, Mahy G, Montgomery GW, Radford-Smith G, Roberts RL, Simms LA, Amininijad L, Cleynen I, Dewit O, Franchimont D, Georges M, Laukens D, Peeters H, Rahier JF, Rutgeerts P, Theatre E, Van Gossum A, Vermeire S, Aumais G, Baidoo L, Barrie AM 3rd, Beck K, Bernard EJ, Binion DG, Bitton A, Brant SR, Cho JH, Cohen A, Croitoru K, Daly MJ, Datta LW, Deslandres C, Duerr RH, Dutridge D, Ferguson J, Fultz J, Goyette P, Greenberg GR, Haritunians T, Jobin G, Katz S, Lahaie RG, McGovern DP, Nelson L, Ng SM, Ning K, Oikonomou I, Paré P, Proctor DD, Regueiro MD, Rioux JD, Ruggiero E, Schumm L, Schwartz M, Scott R, Sharma Y, Silverberg MS, Spears D, Steinhart A, Stempak JM, Swoger JM, Tsagarelis C, Zhang W, Zhang C, Zhao H, Aerts J, Ahmad T, Arbury H, Attwood A, Auton A, Ball SG, Balmforth AJ, Barnes C, Barrett JC, Barroso I, Barton A, Bennett AJ, Bhaskar S, Blaszczyk K, Bowes J, Brand OJ, Braund PS, Bredin F, Breen G, Brown MJ, Bruce IN, Bull J, Burren OS, Burton J, Byrnes J, Caesar S, Cardin N, Clee CM, Coffey AJ, Connell JM, Conrad DF, Cooper JD, Dominiczak AF, Downes K, Drummond HE, Dudakia D, Dunham A, Ebbs B, Eccles D, Edkins S, Edwards C, Elliot A, Emery P, Evans DM, Evans G, Eyre S, Farmer A, Ferrier IN, Flynn E, Forbes A, Forty L, Franklyn JA, Frayling TM, Freathy RM, Giannoulatou E, Gibbs P, Gilbert P, Gordon-Smith K, Gray E, Green E, Groves CJ, Grozeva D, Gwilliam R, Hall A, Hammond N, Hardy M, Harrison P, Hassanali N, Hebaishi H, Hines S, Hinks A, Hitman GA, Hocking L, Holmes C, Howard E, Howard P, Howson JM, Hughes D, Hunt S, Isaacs JD, Jain M, Jewell DP, Johnson T, Jolley JD, Jones IR, Jones LA, Kirov G, Langford CF, Lango-Allen H, Lathrop GM, Lee J, Lee KL, Lees C, Lewis K, Lindgren CM, Maisuria-Armer M, Maller J, Mansfield J, Marchini JL, Martin P, Massey DC, McArdle WL, McGuffin P, McLay KE, McVean G, Mentzer A, Mimmack ML, Morgan AE, Morris AP, Mowat C, Munroe PB, Myers S, Newman W, Nimmo ER, O'Donovan MC, Onipinla A, Ovington NR, Owen MJ, Palin K, Palotie A, Parnell K, Pearson R, Pernet D, Perry JR, Phillips A, Plagnol V, Prescott NJ, Prokopenko I, Quail MA, Rafelt S, Rayner NW, Reid DM, Renwick A, Ring SM, Robertson N, Robson S, Russell E, St Clair D, Sambrook JG, Sanderson JD, Sawcer SJ, Schuilenburg H, Scott CE, Scott R, Seal S, Shaw-Hawkins S, Shields BM, Simmonds MJ, Smyth DJ, Somaskantharajah E, Spanova K, Steer S, Stephens J, Stevens HE, Stirrups K, Stone MA, Strachan DP, Su Z, Symmons DP, Thompson JR, Thomson W, Tobin MD, Travers ME, Turnbull C, Vukcevic D, Wain LV, Walker M, Walker NM, Wallace C, Warren-Perry M, Watkins NA, Webster J, Weedon MN, Wilson AG, Woodburn M, Wordsworth BP, Yau C, Young AH, Zeggini E, Brown MA, Burton PR, Caulfield MJ, Compston A, Farrall M, Gough SC, Hall AS, Hattersley AT, Hill AV, Mathew CG, Pembrey M, Satsangi J, Stratton MR, Worthington J, Hurles ME, Duncanson A, Ouwehand WH, Parkes M, Rahman N, Todd JA, Samani NJ, Kwiatkowski DP, McCarthy MI, Craddock N, Deloukas P, Donnelly P, Blackwell JM, Bramon E, Casas JP, Corvin A, Jankowski J, Markus HS, Palmer CN, Plomin R, Rautanen A, Trembath RC, Viswanathan AC, Wood NW, Spencer CC, Band G, Bellenguez C, Freeman C, Hellenthal G, Giannoulatou E, Pirinen M, Pearson R, Strange A, Blackburn H, Bumpstead SJ, Dronov S, Gillman M, Jayakumar A, McCann OT, Liddle J, Potter SC, Ravindrarajah R, Ricketts M, Waller M, Weston P, Widaa S, Whittaker P.

Author information

1
Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1HH, UK.

Abstract

Crohn's disease and ulcerative colitis, the two common forms of inflammatory bowel disease (IBD), affect over 2.5 million people of European ancestry, with rising prevalence in other populations. Genome-wide association studies and subsequent meta-analyses of these two diseases as separate phenotypes have implicated previously unsuspected mechanisms, such as autophagy, in their pathogenesis and showed that some IBD loci are shared with other inflammatory diseases. Here we expand on the knowledge of relevant pathways by undertaking a meta-analysis of Crohn's disease and ulcerative colitis genome-wide association scans, followed by extensive validation of significant findings, with a combined total of more than 75,000 cases and controls. We identify 71 new associations, for a total of 163 IBD loci, that meet genome-wide significance thresholds. Most loci contribute to both phenotypes, and both directional (consistently favouring one allele over the course of human history) and balancing (favouring the retention of both alleles within populations) selection effects are evident. Many IBD loci are also implicated in other immune-mediated disorders, most notably with ankylosing spondylitis and psoriasis. We also observe considerable overlap between susceptibility loci for IBD and mycobacterial infection. Gene co-expression network analysis emphasizes this relationship, with pathways shared between host responses to mycobacteria and those predisposing to IBD.

PMID:
23128233
PMCID:
PMC3491803
DOI:
10.1038/nature11582
[Indexed for MEDLINE]
Free PMC Article

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