Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis

BF Voight, LJ Scott, V Steinthorsdottir, AP Morris, C Dina, RP Welch, E Zeggini, C Huth, YS Aulchenko, G Thorleifsson, LJ McCulloch, T Ferreira, H Grallert, Najaf Amin, GM Wu, CJ Willer, S Raychaudhuri, SA McCarroll, C Langenberg, OM HofmannJ Dupuis, L Qi, AV Segre, Mandy van Hoek, P Navarro, K Ardlie, B Balkau, R Benediktsson, AJ Bennett, R Blagieva, E Boerwinkle, LL Bonnycastle, KB Bostrom, B Bravenboer, S Bumpstead, NP Burtt, G Charpentier, PS Chines, M Cornelis, DJ Couper, G Crawford, ASF Doney, KS Elliott, AL Elliott, MR Erdos, CS Fox, CS Franklin, M Ganser, C Gieger, N Grarup, T Green, S Griffin, CJ Groves, C Guiducci, S Hadjadj, N Hassanali, Cindy Herder, B Isomaa, AU Jackson, PRV Johnson, T Jorgensen, WHL Kao, N Klopp, A Kong, P Kraft, J Kuusisto, T Lauritzen, M Li, A Lieverse, CM Lindgren, V Lyssenko, M (Michel) Marre, T Meitinger, K Midthjell, MA Morken, N Narisu, P Nilsson, KR Owen, F Payne, JRB Perry, AK Petersen, C Platou, C Proenca, I Prokopenko, W Rathmann, NW Rayner, NR Robertson, G Rocheleau, M Roden, MJ Sampson, R Saxena, BM Shields, P Shrader, G Sigurdsson, T Sparso, K Strassburger, HM Stringham, Q Sun, AJ Swift, B Thorand, J Tichet, T Tuomi, RM van Dam, TW van Haeften, T van Herpt, JV van Vliet-Ostaptchouk, GB Walters, MN Weedon, C Wijmenga, JCM Witteman, RN Bergman, S Cauchi, FS Collins, AL Gloyn, U Gyllensten, T Hansen, WA Hide, GA Hitman, Bert Hofman, DJ Hunter, K Hveem, M Laakso, KL Mohlke, AD Morris, CNA Palmer, PP Pramstaller, I Rudan, E.J.G. Sijbrands, LD Stein, T Jaakko, André Uitterlinden, M Walker, NJ Wareham, RM Watanabe, GR Abecasis, BO Boehm, H Campbell, MJ Daly, AT Hattersley, FB Hu, JB Meigs, JS Pankow, O Pedersen, HE Wichmann, I Barroso, JC Florez, TM Frayling, L Groop, R Sladek, U Thorsteinsdottir, JF Wilson, T Illig, P Froguel, Cornelia Duijn, K Stefansson, D Altshuler, M Boehnke, MI McCarthy

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Abstract

By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P < 5 x 10(-8). These include a second independent signal at the KCNQ1 locus; the first report, to our knowledge, of an X-chromosomal association (near DUSP9); and a further instance of overlap between loci implicated in monogenic and multifactorial forms of diabetes (at HNF1A). The identified loci affect both beta-cell function and insulin action, and, overall, T2D association signals show evidence of enrichment for genes involved in cell cycle regulation. We also show that a high proportion of T2D susceptibility loci harbor independent association signals influencing apparently unrelated complex traits.
Original languageUndefined/Unknown
Pages (from-to)579-U155
JournalNature Genetics
Volume42
Issue number7
DOIs
Publication statusPublished - 2010

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