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

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

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Abstract

Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D)(1-11). 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 similar to 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.
Original languageEnglish
Pages (from-to)638-645
JournalNature Genetics
Volume40
Issue number5
DOIs
Publication statusPublished - 2008

Subject classification (UKÄ)

  • Endocrinology and Diabetes

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