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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2008-03-30

AUTHORS

Eleftheria Zeggini, Laura J Scott, Richa Saxena, Benjamin F Voight, Jonathan L Marchini, Tianle Hu, Paul IW de Bakker, Gonçalo R Abecasis, Peter Almgren, Gitte Andersen, Kristin Ardlie, Kristina Bengtsson Boström, Richard N Bergman, Lori L Bonnycastle, Knut Borch-Johnsen, Noël P Burtt, Hong Chen, Peter S Chines, Mark J Daly, Parimal Deodhar, Chia-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 Jørgensen, 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 NA 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 Sandbæk, 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, Inês Barroso, Andrew T Hattersley, Francis S Collins, Leif Groop, Mark I McCarthy, Michael Boehnke, David Altshuler

ABSTRACT

Genome-wide association (GWA) studies have identified multiple loci at which common variants modestly but reproducibly influence risk of type 2 diabetes (T2D)1,2,3,4,5,6,7,8,9,10,11. 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 ∼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 × 10−14), CDC123-CAMK1D (P = 1.2 × 10−10), TSPAN8-LGR5 (P = 1.1 × 10−9), THADA (P = 1.1 × 10−9), ADAMTS9 (P = 1.2 × 10−8) and NOTCH2 (P = 4.1 × 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. More... »

PAGES

638-645

Journal

TITLE

Nature Genetics

ISSUE

5

VOLUME

40

Author Affiliations

  • Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK
  • Department of Biostatistics and Center for Statistical Genetics, University of Michigan, 48109, Ann Arbor, Michigan, USA
  • Department of Genetics, Harvard Medical School, 02115, Boston, Massachusetts, USA
  • Department of Medicine, Harvard Medical School, 02115, Boston, Massachusetts, USA
  • Department of Statistics, University of Oxford, OX1 3TG, Oxford, UK
  • Division of Genetics, Brigham and Women's Hospital, Harvard-Partners Center for Genetics and Genomics, 02115, Boston, Massachusetts, USA
  • Department of Clinical Sciences, Diabetes and Endocrinology Research Unit, University Hospital Malmö, Lund University, S-205 02, Malmö, Sweden
  • Steno Diabetes Center, DK-2820, Copenhagen, Denmark
  • Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), 02142, Cambridge, Massachusetts, USA
  • Skaraborg Institute, S-541 30, Skövde, Sweden
  • Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, 90033, Los Angeles, California, USA
  • Genome Technology Branch, National Human Genome Research Institute, 20892, Bethesda, Maryland, USA
  • Faculty of Health Science, University of Aarhus, DK-8000, Aarhus, Denmark
  • Diabetes and Metabolism Disease Area, Novartis Institutes for BioMedical Research, 100 Technology Square, 02139, Cambridge, Massachusetts, USA
  • Division of Medicine and Therapeutics, Diabetes Research Group, Ninewells Hospital and Medical School, DD1 9SY, Dundee, UK
  • Diabetes Genetics, Institute of Biomedical and Clinical Science, Peninsula Medical School, Barrack Road, EX2 5DW, Exeter, UK
  • Gesellschaft für Strahlenforschung-National Research Center for Environment and Health, Institute of Epidemiology, D-85764, Neuherberg, Germany
  • Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, OX3 7LJ, Oxford, UK
  • Institute for Clinical Diabetes Research, German Diabetes Center, Leibniz Institute at Heinrich Heine University, D-40225, Düsseldorf, Germany
  • Centre for Diabetes and Metabolic Medicine, Barts and The London, Royal London Hospital, E1 1BB, Whitechapel, London, UK
  • Folkhälsan Research Center, FIN-00014, Helsinki, Finland
  • Research Centre for Prevention and Health, Glostrup University Hospital, DK-2600, Glostrup, Denmark
  • deCODE genetics, Sturlugata 8, IS-101, Reykjavik, Iceland
  • Department of Molecular Biology, Massachusetts General Hospital, 02114, Boston, Massachusetts, USA
  • Department of Medicine, University of Kuopio and Kuopio University Hospital, 70210, Kuopio, Finland
  • MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, CB2 0QQ, Cambridge, UK
  • Department of General Practice, University of Aarhus, DK-8000, Aarhus, Denmark
  • Department of Genetics, University of North Carolina, 27599, Chapel Hill, North Carolina, USA
  • Department of Public Health and General Practice, HUNT Research Centre, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), 7650, Verdal, Norway
  • Population Pharmacogenetics Group, Biomedical Research Centre, Ninewells Hospital and Medical School, DD1 9SY, Dundee, UK
  • Metabolic Disease Group, Wellcome Trust Sanger Institute, CB10 1SA, Hinxton, Cambridge, UK
  • Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology (NTNU), N-7600, Levanger, Norway
  • Department of Medicine, Channing Laboratory, Brigham and Women's Hospital and Harvard Medical School, 02115, Boston, Massachusetts, USA
  • The MRC Centre for Causal Analyses in Translational Epidemiology, Bristol University, Canynge Hall, Whiteladies Road, BS2 8PR, Bristol, UK
  • Department of Medicine, Helsinki University Hospital, University of Helsinki, FIN-00300, Helsinki, Finland
  • South Ostrobothnia Central Hospital, 60220, Seinäjoki, Finland
  • Diabetes Research Group, School of Clinical Medical Sciences, Newcastle University, Framlington Place, NE2 4HH, Newcastle upon Tyne, UK
  • Department of Preventative Medicine, Keck School of Medicine, University of Southern California, 90033, Los Angeles, California, USA
  • Diabetes Unit, Massachusetts General Hospital, 02114, Boston, Massachusetts, USA
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng.120

    DOI

    http://dx.doi.org/10.1038/ng.120

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1006325160

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/18372903


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