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Research Article

Stratifying Type 2 Diabetes Cases by BMI Identifies Genetic Risk Variants in LAMA1 and Enrichment for Risk Variants in Lean Compared to Obese Cases

  • John R. B. Perry,

    Affiliations: Genetics of Complex Traits, Peninsula Medical School, University of Exeter, Exeter, United Kingdom, Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom, Department of Twin Research and Genetic Epidemiology, King's College London, London, United Kingdom

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  • Benjamin F. Voight,

    Affiliation: Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America

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  • Loïc Yengo,

    Affiliation: CNRS UMR 8199, Genomics of Metabolic Diseases, Lille, France

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  • Najaf Amin,

    Affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands

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  • Josée Dupuis,

    Affiliations: Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, United States of America, National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, United States of America

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  • Martha Ganser,

    Affiliation: Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, United States of America

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  • Harald Grallert,

    Affiliation: Research Unit of Molecular Epidemiology, Helmholtz Zentrum Muenchen, Neuherberg, Germany

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  • Pau Navarro,

    Affiliation: MRC Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom

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  • Man Li,

    Affiliation: Johns Hopkins Bloomberg School of Public Health and Epidemiology, Baltimore, Maryland, United States of America

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  • Lu Qi,

    Affiliation: Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America

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  • Valgerdur Steinthorsdottir,

    Affiliation: deCODE Genetics, Reykjavik, Iceland

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  • Robert A. Scott,

    Affiliation: MRC Epidemiology Unit, Medical Research Council, Cambridge, United Kingdom

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  • Peter Almgren,

    Affiliation: Diabetes and Endocrinology Research Unit, Department of Clinical Sciences, Lund University, Malmoe, Sweden

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  • Dan E. Arking,

    Affiliation: McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, United States of America

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  • Yurii Aulchenko,

    Affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands

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  • Beverley Balkau,

    Affiliation: INSERM CESP U1018, Villejuif, France

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  • Rafn Benediktsson,

    Affiliations: Landspitali University Hospital, Reykjavik, Iceland, Icelandic Heart Association, Kopavogur, Iceland

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  • Richard N. Bergman,

    Affiliation: Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, California, United States of America

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  • Eric Boerwinkle,

    Affiliation: University of Texas Health Science Center at Houston, Human Genetics Center, Houston, Texas, United States of America

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  • Lori Bonnycastle,

    Affiliation: National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America

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  • Noël P. Burtt,

    Affiliation: Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America

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  • Harry Campbell,

    Affiliation: Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh, United Kingdom

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  • Guillaume Charpentier,

    Affiliation: Corbeil-Essonnes hospital, Department of Endocrinology-Diabetology, Corbeil-Essonnes, France

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  • Francis S. Collins,

    Affiliation: National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, United States of America

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  • Christian Gieger,

    Affiliation: Institute of Genetic Epidemiology, Helmholtz Zentrum Muenchen, Neuherberg, Germany

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  • Todd Green,

    Affiliation: Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America

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  • Samy Hadjadj,

    Affiliation: CHU Poitiers, Department of Endocrinology-Diabetology, CIC INSERM 0801, INSERM U927, University of Medical and Pharmaceutical Sciences, Poitiers, France

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  • Andrew T. Hattersley,

    Affiliation: Genetics of Complex Traits, Peninsula Medical School, University of Exeter, Exeter, United Kingdom

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  • Christian Herder,

    Affiliation: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany

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  • Albert Hofman,

    Affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands

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  • Andrew D. Johnson,

    Affiliation: National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, United States of America

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  • Anna Kottgen,

    Affiliations: Johns Hopkins Bloomberg School of Public Health and Epidemiology, Baltimore, Maryland, United States of America, Freiburg University Clinic, Renal Division, Freiburg, Germany

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  • Peter Kraft,

    Affiliation: Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America

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  • Yann Labrune,

    Affiliation: CNRS UMR 8199, Genomics of Metabolic Diseases, Lille, France

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  • Claudia Langenberg,

    Affiliation: MRC Epidemiology Unit, Medical Research Council, Cambridge, United Kingdom

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  • Alisa K. Manning,

    Affiliation: Boston University School of Public Health, Boston, Massachusetts, United States of America

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  • Karen L. Mohlke,

    Affiliation: Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, United States of America

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  • Andrew P. Morris,

    Affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom

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  • Ben Oostra,

    Affiliation: Erasmus University Medical School, Rotterdam, The Netherlands

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  • James Pankow,

    Affiliation: School of Public Health, Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, Minnesota, United States of America

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  • Ann-Kristin Petersen,

    Affiliation: Institute of Genetic Epidemiology, Helmholtz Zentrum Muenchen, Neuherberg, Germany

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  • Peter P. Pramstaller,

    Affiliations: Center for Biomedicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy (Affiliated Institute of the University of Lübeck, Lübeck, Germany), Department of Neurology, General Central Hospital, Bolzano, Italy, Department of Neurology, University of Lübeck, Lübeck, Germany

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  • Inga Prokopenko,

    Affiliations: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom, Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Oxford, United Kingdom

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  • Wolfgang Rathmann,

    Affiliation: Institute of Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany

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  • William Rayner,

    Affiliation: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom

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  • Michael Roden,

    Affiliations: Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research, Heinrich Heine University Düsseldorf, Düsseldorf, Germany, Department of Metabolic Diseases, University Hospital Düsseldorf, Düsseldorf, Germany

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  • Igor Rudan,

    Affiliation: Centre for Population Health Sciences, University of Edinburgh, Edinburgh, United Kingdom

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  • Denis Rybin,

    Affiliation: Boston University Data Coordinating Center, Boston, Massachusetts, United States of America

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  • Laura J. Scott,

    Affiliation: Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, United States of America

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  • Gunnar Sigurdsson,

    Affiliations: Landspitali University Hospital, Reykjavik, Iceland, Icelandic Heart Association, Kopavogur, Iceland

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  • Rob Sladek,

    Affiliation: Department of Human Genetics, Faculty of Medicine, McGill University, Montreal, Canada

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  • Gudmar Thorleifsson,

    Affiliation: deCODE Genetics, Reykjavik, Iceland

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  • Unnur Thorsteinsdottir,

    Affiliations: deCODE Genetics, Reykjavik, Iceland, Faculty of Medicine, University of Iceland, Reykjavík, Iceland

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  • Jaakko Tuomilehto,

    Affiliations: Diabetes Prevention Unit, National Institute for Health and Welfare, Helsinki, Finland, South Ostrobothnia Central Hospital, Seinäjoki, Finland, Red RECAVA Grupo RD06/0014/0015, Hospital Universitario La Paz, Madrid, Spain, Centre for Vascular Prevention, Danube-University Krems, Krems, Austria

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  • Andre G. Uitterlinden,

    Affiliation: Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands

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  • Sidonie Vivequin,

    Affiliation: CNRS UMR 8199, Genomics of Metabolic Diseases, Lille, France

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  • Michael N. Weedon,

    Affiliation: Genetics of Complex Traits, Peninsula Medical School, University of Exeter, Exeter, United Kingdom

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  • Alan F. Wright,

    Affiliation: MRC Human Genetics Unit, Medical Research Council Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, United Kingdom

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  • MAGIC,
  • DIAGRAM Consortium,
  • GIANT Consortium,
  • Frank B. Hu,

    Affiliation: Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America

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  • Thomas Illig,

    Affiliations: Research Unit of Molecular Epidemiology, Helmholtz Zentrum Muenchen, Neuherberg, Germany, Hannover Unified Biobank, Hannover Medical School, Hannover, Germany

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  • Linda Kao,

    Affiliation: Johns Hopkins Bloomberg School of Public Health and Epidemiology, Baltimore, Maryland, United States of America

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  • James B. Meigs,

    Affiliation: General Medicine Division, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts, United States of America

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  • James F. Wilson,

    Affiliation: Centre for Population Health Sciences, University of Edinburgh, Teviot Place, Edinburgh, United Kingdom

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  • Kari Stefansson,

    Affiliations: deCODE Genetics, Reykjavik, Iceland, Faculty of Medicine, University of Iceland, Reykjavík, Iceland

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  • Cornelia van Duijn,

    Affiliation: Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands

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  • David Altschuler,

    Affiliation: Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America

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  • Andrew D. Morris,

    Affiliation: Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom

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  • Michael Boehnke,

    Affiliation: Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, United States of America

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  • Mark I. McCarthy,

    Affiliations: Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, United Kingdom, Oxford Centre for Diabetes, Endocrinology, and Metabolism, University of Oxford, Oxford, United Kingdom, Oxford NIHR Biomedical Research Centre, Churchill Hospital, Oxford, United Kingdom

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  • Philippe Froguel,

    Affiliations: CNRS UMR 8199, Genomics of Metabolic Diseases, Lille, France, Department of Genomics of Common Diseases, Hammersmith Hospital, Imperial College London, London, United Kingdom

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  • Colin N. A. Palmer,

    Affiliation: Biomedical Research Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, United Kingdom

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  • Nicholas J. Wareham,

    Affiliation: MRC Epidemiology Unit, Medical Research Council, Cambridge, United Kingdom

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  • Leif Groop,

    Affiliation: Diabetes and Endocrinology Research Unit, Department of Clinical Sciences, Lund University, Malmoe, Sweden

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  • Timothy M. Frayling equal contributor mail,

    equal contributor Contributed equally to this work with: Timothy M. Frayling, Stéphane Cauchi

    tim.frayling@pms.ac.uk (TM Frayling); Stephane.Cauchi@good.ibl.fr (S Cauchi)

    Affiliation: Genetics of Complex Traits, Peninsula Medical School, University of Exeter, Exeter, United Kingdom

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  • Stéphane Cauchi equal contributor mail

    equal contributor Contributed equally to this work with: Timothy M. Frayling, Stéphane Cauchi

    tim.frayling@pms.ac.uk (TM Frayling); Stephane.Cauchi@good.ibl.fr (S Cauchi)

    Affiliation: CNRS UMR 8199, Genomics of Metabolic Diseases, Lille, France

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  • Published: May 31, 2012
  • DOI: 10.1371/journal.pgen.1002741

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