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Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes.

Zeggini, Eleftheria and Scott, Laura J and Saxena, Richa and Voight, Benjamin F and Marchini, Jonathan L and Hu, Tianle and de Bakker, Paul I W and Abecasis, Gonçalo R and Almgren, Peter and Andersen, Gitte and Ardlie, Kristin and Boström, Kristina Bengtsson and Bergman, Richard N and Bonnycastle, Lori L and Borch-Johnsen, Knut and Burtt, Noël P and Chen, Hong and Chines, Peter S and Daly, Mark J and Deodhar, Parimal and Ding, Chia-Jen and Doney, Alex S F and Duren, William L and Elliott, Katherine S and Erdos, Michael R and Frayling, Timothy M and Freathy, Rachel M and Gianniny, Lauren and Grallert, Harald and Grarup, Niels and Groves, Christopher J and Guiducci, Candace and Hansen, Torben and Herder, Christian and Hitman, Graham A and Hughes, Thomas and Isomaa, Bo and Jackson, Anne U and Jorgensen, Torben and Kong, Augustine and Kubalanza, Kari and Kuruvilla, Finny G and Kuusisto, Johanna and Langenberg, Claudia and Lango, Hana and Lauritzen, Torsten and Li, Yun and Lindgren, Cecilia M and Lyssenko, Valeriya and Marvelle, Amanda F and Meisinger, Christa and Midthjell, Kristian and Mohlke, Karen L and Morken, Mario A and Morris, Andrew D and Narisu, Narisu and Nilsson, Peter and Owen, Katharine R and Palmer, Colin N A and Payne, Felicity and Perry, John R B and Pettersen, Elin and Platou, Carl and Prokopenko, Inga and Qi, Lu and Qin, Li and Rayner, Nigel W and Rees, Matthew and Roix, Jeffrey and Sandbaek, Anelli and Shields, Beverley and Sjögren, Marketa and Steinthorsdottir, Valgerdur and Stringham, Heather M and Swift, Amy J and Thorleifsson, Gudmar and Thorsteinsdottir, Unnur and Timpson, Nicholas J and Tuomi, Tiinamaija and Tuomilehto, Jaakko and Walker, Mark and Watanabe, Richard M and Weedon, Michael N and Willer, Cristen J and Illig, Thomas and Hveem, Kristian and Hu, Frank B and Laakso, Markku and Stefansson, Kari and Pedersen, Oluf and Wareham, Nicholas J and Barroso, Inês and Hattersley, Andrew T and Collins, Francis S and Groop, Leif and McCarthy, Mark I and Boehnke, Michael and Altshuler, David (2008) Meta-analysis of genome-wide association data and large-scale replication identifies additional susceptibility loci for type 2 diabetes. Nature Genetics, 40 (5). pp. 638-645. ISSN 1546-1718


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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Date Deposited: 14 Dec 2009 13:51
Last Modified: 14 Dec 2009 13:51


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