-
- Robert A. Scott
- MRC Epidemiology Unit, University of Cambridge, Cambridge, U.K.
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- Laura J. Scott
- Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI
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- Reedik Mägi
- Estonian Genome Center, University of Tartu, Tartu, Estonia
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- Letizia Marullo
- Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy
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- Kyle J. Gaulton
- Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, U.K.
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- Marika Kaakinen
- Department of Genomics of Common Disease, Imperial College London, London, U.K.
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- Natalia Pervjakova
- Estonian Genome Center, University of Tartu, Tartu, Estonia
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- Tune H. Pers
- Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA
-
- Andrew D. Johnson
- Framingham Heart Study, Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Framingham, MA
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- John D. Eicher
- Framingham Heart Study, Population Sciences Branch, Division of Intramural Research, National Heart, Lung, and Blood Institute, Framingham, MA
-
- Anne U. Jackson
- Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI
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- Teresa Ferreira
- Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, U.K.
-
- Yeji Lee
- Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI
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- Clement Ma
- Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI
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- Valgerdur Steinthorsdottir
- deCODE genetics, Amgen, Inc., Reykjavik, Iceland
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- Gudmar Thorleifsson
- deCODE genetics, Amgen, Inc., Reykjavik, Iceland
-
- Lu Qi
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA
-
- Natalie R. Van Zuydam
- Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, U.K.
-
- Anubha Mahajan
- Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, U.K.
-
- Han Chen
- Human Genetics Center and Department of Epidemiology, Human Genetics & Environmental Sciences, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX
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- Peter Almgren
- Lund University Diabetes Centre and Department of Clinical Sciences Malmö, University Hospital Scania, Lund University, Malmö, Sweden
-
- Ben F. Voight
- Department of Pharmacology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
-
- Harald Grallert
- Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
-
- Martina Müller-Nurasyid
- Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
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- Janina S. Ried
- Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
-
- Nigel W. Rayner
- Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, U.K.
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- Neil Robertson
- Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, U.K.
-
- Lennart C. Karssen
- Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands
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- Elisabeth M. van Leeuwen
- Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands
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- Sara M. Willems
- MRC Epidemiology Unit, University of Cambridge, Cambridge, U.K.
-
- Christian Fuchsberger
- Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI
-
- Phoenix Kwan
- Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI
-
- Tanya M. Teslovich
- Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI
-
- Pritam Chanda
- High Throughput Biology Center, Johns Hopkins University School of Medicine, Baltimore, MD
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- Man Li
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
-
- Yingchang Lu
- The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY
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- Christian Dina
- l'institut du thorax, INSERM, CNRS, Centre Hospitalier Universitaire de Nantes, Université de Nantes, Nantes, France
-
- Dorothee Thuillier
- Lille Institute of Biology, European Genomics Institute of Diabetes, Lille, France
-
- Loic Yengo
- Lille Institute of Biology, European Genomics Institute of Diabetes, Lille, France
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- Longda Jiang
- Department of Genomics of Common Disease, Imperial College London, London, U.K.
-
- Thomas Sparso
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
-
- Hans A. Kestler
- Leibniz Institute on Aging, Fritz Lipmann Institute, Jena, Germany
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- Himanshu Chheda
- Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland
-
- Lewin Eisele
- Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, Essen, Germany
-
- Stefan Gustafsson
- Molecular Epidemiology, Department of Medical Sciences, and Science for Life Laboratory, Uppsala University, Uppsala, Sweden
-
- Mattias Frånberg
- Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
-
- Rona J. Strawbridge
- Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
-
- Rafn Benediktsson
- Faculty of Medicine, University of Iceland, Reykjavik, Iceland
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- Astradur B. Hreidarsson
- Landspítali University Hospital, Reykjavik, Iceland
-
- Augustine Kong
- deCODE genetics, Amgen, Inc., Reykjavik, Iceland
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- Gunnar Sigurðsson
- Landspítali University Hospital, Reykjavik, Iceland
-
- Nicola D. Kerrison
- MRC Epidemiology Unit, University of Cambridge, Cambridge, U.K.
-
- Jian'an Luan
- MRC Epidemiology Unit, University of Cambridge, Cambridge, U.K.
-
- Liming Liang
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA
-
- Thomas Meitinger
- Munich Heart Alliance, German Centre for Cardiovascular Disease, Munich, Germany
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- Michael Roden
- German Center for Diabetes Research, Neuherberg, Germany
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- Barbara Thorand
- Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
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- Tõnu Esko
- Estonian Genome Center, University of Tartu, Tartu, Estonia
-
- Evelin Mihailov
- Estonian Genome Center, University of Tartu, Tartu, Estonia
-
- Caroline Fox
- Framingham Heart Study, National Heart, Lung, and Blood Institute, Framingham, MA
-
- Ching-Ti Liu
- Department of Biostatistics, Boston University School of Public Health, Boston, MA
-
- Denis Rybin
- Data Coordinating Center, Boston University School of Public Health, Boston, MA
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- Bo Isomaa
- Folkhälsan Research Center, Helsinki, Finland
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- Valeriya Lyssenko
- Lund University Diabetes Centre and Department of Clinical Sciences Malmö, University Hospital Scania, Lund University, Malmö, Sweden
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- Tiinamaija Tuomi
- Folkhälsan Research Center, Helsinki, Finland
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- David J. Couper
- Collaborative Studies Coordinating Center, Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC
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- James S. Pankow
- Division of Epidemiology & Community Health, University of Minnesota, Minneapolis, MN
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- Niels Grarup
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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- Christian T. Have
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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- Marit E. Jørgensen
- Steno Diabetes Center, Gentofte, Denmark
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- Torben Jørgensen
- Research Centre for Prevention and Health, Capital Region of Denmark, Copenhagen, Denmark
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- Allan Linneberg
- Research Centre for Prevention and Health, Capital Region of Denmark, Copenhagen, Denmark
-
- Marilyn C. Cornelis
- Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL
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- Rob M. van Dam
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA
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- David J. Hunter
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA
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- Peter Kraft
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA
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- Qi Sun
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA
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- Sarah Edkins
- Wellcome Trust Sanger Institute, Hinxton, U.K.
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- Katharine R. Owen
- Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, U.K.
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- John R.B. Perry
- MRC Epidemiology Unit, University of Cambridge, Cambridge, U.K.
-
- Andrew R. Wood
- Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, U.K.
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- Eleftheria Zeggini
- Wellcome Trust Sanger Institute, Hinxton, U.K.
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- Juan Tajes-Fernandes
- Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, U.K.
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- Goncalo R. Abecasis
- Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI
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- Lori L. Bonnycastle
- National Human Genome Research Institute, National Institutes of Health, Bethesda, MD
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- Peter S. Chines
- National Human Genome Research Institute, National Institutes of Health, Bethesda, MD
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- Heather M. Stringham
- Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI
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- Heikki A. Koistinen
- Department of Health, National Institute for Health and Welfare, Helsinki, Finland
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- Leena Kinnunen
- Department of Health, National Institute for Health and Welfare, Helsinki, Finland
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- Bengt Sennblad
- Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
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- Thomas W. Mühleisen
- Institute of Human Genetics, University of Bonn, Bonn, Germany
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- Markus M. Nöthen
- Institute of Human Genetics, University of Bonn, Bonn, Germany
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- Sonali Pechlivanis
- Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, Essen, Germany
-
- Damiano Baldassarre
- Centro Cardiologico Monzino, Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy
-
- Karl Gertow
- Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
-
- Steve E. Humphries
- Cardiovascular Genetics, BHF Laboratories, Institute Cardiovascular Sciences, University College London, London, U.K.
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- Elena Tremoli
- Centro Cardiologico Monzino, Istituto di Ricovero e Cura a Carattere Scientifico, Milan, Italy
-
- Norman Klopp
- Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
-
- Julia Meyer
- Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
-
- Gerald Steinbach
- Department of Clinical Chemistry and Central Laboratory, University of Ulm, Ulm, Germany
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- Roman Wennauer
- Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands
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- Johan G. Eriksson
- Folkhälsan Research Center, Helsinki, Finland
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- Satu Mӓnnistö
- Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland
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- Leena Peltonen
- Wellcome Trust Sanger Institute, Hinxton, U.K.
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- Emmi Tikkanen
- Institute for Molecular Medicine Finland, University of Helsinki, Helsinki, Finland
-
- Guillaume Charpentier
- Endocrinology-Diabetology Unit, Corbeil-Essonnes Hospital, Corbeil-Essonnes, France
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- Elodie Eury
- CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, University of Lille, Lille, France
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- Stéphane Lobbens
- CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille, University of Lille, Lille, France
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- Bruna Gigante
- Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
-
- Karin Leander
- Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
-
- Olga McLeod
- Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
-
- Erwin P. Bottinger
- The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY
-
- Omri Gottesman
- The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY
-
- Douglas Ruderfer
- Division of Psychiatric Genomics, Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY
-
- Matthias Blüher
- IFB AdiposityDiseases, University of Leipzig, Leipzig, Germany
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- Peter Kovacs
- IFB AdiposityDiseases, University of Leipzig, Leipzig, Germany
-
- Anke Tonjes
- IFB AdiposityDiseases, University of Leipzig, Leipzig, Germany
-
- Nisa M. Maruthur
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD
-
- Chiara Scapoli
- Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy
-
- Raimund Erbel
- Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, Essen, Germany
-
- Karl-Heinz Jöckel
- Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, Essen, Germany
-
- Susanne Moebus
- Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, Essen, Germany
-
- Ulf de Faire
- Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
-
- Anders Hamsten
- Cardiovascular Medicine Unit, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
-
- Michael Stumvoll
- IFB AdiposityDiseases, University of Leipzig, Leipzig, Germany
-
- Panagiotis Deloukas
- Wellcome Trust Sanger Institute, Hinxton, U.K.
-
- Peter J. Donnelly
- Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, U.K.
-
- Timothy M. Frayling
- Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, U.K.
-
- Andrew T. Hattersley
- Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, U.K.
-
- Samuli Ripatti
- Wellcome Trust Sanger Institute, Hinxton, U.K.
-
- Veikko Salomaa
- Department of Health, National Institute for Health and Welfare, Helsinki, Finland
-
- Nancy L. Pedersen
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
-
- Bernhard O. Boehm
- Division of Endocrinology and Diabetes, Department of Internal Medicine, University Medical Centre Ulm, Ulm, Germany
-
- Richard N. Bergman
- Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA
-
- Francis S. Collins
- National Human Genome Research Institute, National Institutes of Health, Bethesda, MD
-
- Karen L. Mohlke
- Department of Genetics, University of North Carolina, Chapel Hill, NC
-
- Jaakko Tuomilehto
- Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland
-
- Torben Hansen
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
-
- Oluf Pedersen
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
-
- Inês Barroso
- Wellcome Trust Sanger Institute, Hinxton, U.K.
-
- Lars Lannfelt
- Department of Public Health and Caring Sciences, Uppsala University, Uppsala, Sweden
-
- Erik Ingelsson
- Molecular Epidemiology, Department of Medical Sciences, and Science for Life Laboratory, Uppsala University, Uppsala, Sweden
-
- Lars Lind
- Cardiovascular Epidemiology, Department of Medical Sciences, Uppsala University Hospital, Uppsala, Sweden
-
- Cecilia M. Lindgren
- Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, U.K.
-
- Stephane Cauchi
- Lille Institute of Biology, European Genomics Institute of Diabetes, Lille, France
-
- Philippe Froguel
- Department of Genomics of Common Disease, Imperial College London, London, U.K.
-
- Ruth J.F. Loos
- The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY
-
- Beverley Balkau
- INSERM, CESP, UMR 1018, Villejuif, France
-
- Heiner Boeing
- German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany
-
- Paul W. Franks
- Lund University, Malmö, Sweden
-
- Aurelio Barricarte Gurrea
- Navarra Public Health Institute, Pamplona, Spain
-
- Domenico Palli
- Cancer Research and Prevention Institute, Florence, Italy
-
- Yvonne T. van der Schouw
- University Medical Center Utrecht, Utrecht, the Netherlands
-
- David Altshuler
- Broad Institute of MIT and Harvard, Cambridge, MA
-
- Leif C. Groop
- Lund University Diabetes Centre and Department of Clinical Sciences Malmö, University Hospital Scania, Lund University, Malmö, Sweden
-
- Claudia Langenberg
- MRC Epidemiology Unit, University of Cambridge, Cambridge, U.K.
-
- Nicholas J. Wareham
- MRC Epidemiology Unit, University of Cambridge, Cambridge, U.K.
-
- Eric Sijbrands
- Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands
-
- Cornelia M. van Duijn
- Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands
-
- Jose C. Florez
- Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA
-
- James B. Meigs
- Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA
-
- Eric Boerwinkle
- Human Genetics Center, The University of Texas Health Science Center at Houston, Houston, TX
-
- Christian Gieger
- Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
-
- Konstantin Strauch
- Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
-
- Andres Metspalu
- Estonian Genome Center, University of Tartu, Tartu, Estonia
-
- Andrew D. Morris
- Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Edinburgh, U.K.
-
- Colin N.A. Palmer
- Pat Macpherson Centre for Pharmacogenetics and Pharmacogenomics and Biomedical Research Institute, Ninewells Hospital, University of Dundee, Dundee, U.K.
-
- Frank B. Hu
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA
-
- Unnur Thorsteinsdottir
- deCODE genetics, Amgen, Inc., Reykjavik, Iceland
-
- Kari Stefansson
- deCODE genetics, Amgen, Inc., Reykjavik, Iceland
-
- Josée Dupuis
- Framingham Heart Study, National Heart, Lung, and Blood Institute, Framingham, MA
-
- Andrew P. Morris
- Estonian Genome Center, University of Tartu, Tartu, Estonia
-
- Michael Boehnke
- Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI
-
- Mark I. McCarthy
- Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, U.K.
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- Inga Prokopenko
- Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, U.K.
抄録
<jats:p>To characterize type 2 diabetes (T2D)-associated variation across the allele frequency spectrum, we conducted a meta-analysis of genome-wide association data from 26,676 T2D case and 132,532 control subjects of European ancestry after imputation using the 1000 Genomes multiethnic reference panel. Promising association signals were followed up in additional data sets (of 14,545 or 7,397 T2D case and 38,994 or 71,604 control subjects). We identified 13 novel T2D-associated loci (P < 5 × 10−8), including variants near the GLP2R, GIP, and HLA-DQA1 genes. Our analysis brought the total number of independent T2D associations to 128 distinct signals at 113 loci. Despite substantially increased sample size and more complete coverage of low-frequency variation, all novel associations were driven by common single nucleotide variants. Credible sets of potentially causal variants were generally larger than those based on imputation with earlier reference panels, consistent with resolution of causal signals to common risk haplotypes. Stratification of T2D-associated loci based on T2D-related quantitative trait associations revealed tissue-specific enrichment of regulatory annotations in pancreatic islet enhancers for loci influencing insulin secretion and in adipocytes, monocytes, and hepatocytes for insulin action–associated loci. These findings highlight the predominant role played by common variants of modest effect and the diversity of biological mechanisms influencing T2D pathophysiology.</jats:p>
収録刊行物
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- Diabetes
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Diabetes 66 (11), 2888-2902, 2017-05-31
American Diabetes Association