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Nat Genet. 2012 Dec;44(12):1294-301. doi: 10.1038/ng.2435. Epub 2012 Oct 28.

Bayesian refinement of association signals for 14 loci in 3 common diseases.

Collaborators (205)

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.

Abstract

To further investigate susceptibility loci identified by genome-wide association studies, we genotyped 5,500 SNPs across 14 associated regions in 8,000 samples from a control group and 3 diseases: type 2 diabetes (T2D), coronary artery disease (CAD) and Graves' disease. We defined, using Bayes theorem, credible sets of SNPs that were 95% likely, based on posterior probability, to contain the causal disease-associated SNPs. In 3 of the 14 regions, TCF7L2 (T2D), CTLA4 (Graves' disease) and CDKN2A-CDKN2B (T2D), much of the posterior probability rested on a single SNP, and, in 4 other regions (CDKN2A-CDKN2B (CAD) and CDKAL1, FTO and HHEX (T2D)), the 95% sets were small, thereby excluding most SNPs as potentially causal. Very few SNPs in our credible sets had annotated functions, illustrating the limitations in understanding the mechanisms underlying susceptibility to common diseases. Our results also show the value of more detailed mapping to target sequences for functional studies.

PMID:
23104008
[PubMed - indexed for MEDLINE]
PMCID:
PMC3791416
Free PMC Article
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