Zeggini Eleftheria, Scott Laura J, Saxena Richa, Voight Benjamin F, Marchini Jonathan L, Hu Tianle, de Bakker Paul I W, Abecasis Gonçalo R, Almgren Peter, Andersen Gitte, Ardlie Kristin, Boström Kristina Bengtsson, Bergman Richard N, Bonnycastle Lori L, Borch-Johnsen Knut, Burtt Noël P, Chen Hong, Chines Peter S, Daly Mark J, Deodhar Parimal, Ding Chia-Jen, Doney Alex S F, Duren William L, Elliott Katherine S, Erdos Michael R, Frayling Timothy M, Freathy Rachel M, Gianniny Lauren, Grallert Harald, Grarup Niels, Groves Christopher J, Guiducci Candace, Hansen Torben, Herder Christian, Hitman Graham A, Hughes Thomas E, Isomaa Bo, Jackson Anne U, Jørgensen Torben, Kong Augustine, Kubalanza Kari, Kuruvilla Finny G, Kuusisto Johanna, Langenberg Claudia, Lango Hana, Lauritzen Torsten, Li Yun, Lindgren Cecilia M, Lyssenko Valeriya, Marvelle Amanda F, Meisinger Christa, Midthjell Kristian, Mohlke Karen L, Morken Mario A, Morris Andrew D, Narisu Narisu, Nilsson Peter, Owen Katharine R, Palmer Colin N A, Payne Felicity, Perry John R B, Pettersen Elin, Platou Carl, Prokopenko Inga, Qi Lu, Qin Li, Rayner Nigel W, Rees Matthew, Roix Jeffrey J, Sandbaek Anelli, Shields Beverley, Sjögren Marketa, Steinthorsdottir Valgerdur, Stringham Heather M, Swift Amy J, Thorleifsson Gudmar, Thorsteinsdottir Unnur, Timpson Nicholas J, Tuomi Tiinamaija, Tuomilehto Jaakko, Walker Mark, Watanabe Richard M, Weedon Michael N, Willer Cristen J, Illig Thomas, Hveem Kristian, Hu Frank B, Laakso Markku, Stefansson Kari, Pedersen Oluf, Wareham Nicholas J, Barroso Inês, Hattersley Andrew T, Collins Francis S, Groop Leif, McCarthy Mark I, Boehnke Michael, Altshuler David
Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Nat Genet. 2008 May;40(5):638-45. doi: 10.1038/ng.120. Epub 2008 Mar 30.
Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D). Established associations to common and rare variants explain only a small proportion of the heritability of T2D. As previously published analyses had limited power to identify variants with modest effects, we carried out meta-analysis of three T2D GWA scans comprising 10,128 individuals of European descent and approximately 2.2 million SNPs (directly genotyped and imputed), followed by replication testing in an independent sample with an effective sample size of up to 53,975. We detected at least six previously unknown loci with robust evidence for association, including the JAZF1 (P = 5.0 x 10(-14)), CDC123-CAMK1D (P = 1.2 x 10(-10)), TSPAN8-LGR5 (P = 1.1 x 10(-9)), THADA (P = 1.1 x 10(-9)), ADAMTS9 (P = 1.2 x 10(-8)) and NOTCH2 (P = 4.1 x 10(-8)) gene regions. Our results illustrate the value of large discovery and follow-up samples for gaining further insights into the inherited basis of T2D.
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