IDEAS home Printed from https://ideas.repec.org/a/nat/nature/v536y2016i7614d10.1038_nature18642.html
   My bibliography  Save this article

The genetic architecture of type 2 diabetes

Author

Listed:
  • Christian Fuchsberger

    (University of Michigan
    Molecular and Clinical Pharmacology, Medical University of Innsbruck
    Center for Biomedicine, European Academy of Bolzano/Bozen (EURAC), affiliated with the University of Lübeck)

  • Jason Flannick

    (Program in Medical and Population Genetics, Broad Institute
    Massachusetts General Hospital)

  • Tanya M. Teslovich

    (University of Michigan)

  • Anubha Mahajan

    (Wellcome Trust Centre for Human Genetics, University of Oxford)

  • Vineeta Agarwala

    (Program in Medical and Population Genetics, Broad Institute
    Massachusetts Institute of Technology)

  • Kyle J. Gaulton

    (Wellcome Trust Centre for Human Genetics, University of Oxford)

  • Clement Ma

    (University of Michigan
    † Present addresses are provided in the Supplementary Information.)

  • Pierre Fontanillas

    (Program in Medical and Population Genetics, Broad Institute
    † Present addresses are provided in the Supplementary Information.)

  • Loukas Moutsianas

    (Wellcome Trust Centre for Human Genetics, University of Oxford
    † Present addresses are provided in the Supplementary Information.)

  • Davis J. McCarthy

    (Wellcome Trust Centre for Human Genetics, University of Oxford
    University of Oxford)

  • Manuel A. Rivas

    (Wellcome Trust Centre for Human Genetics, University of Oxford)

  • John R. B. Perry

    (Wellcome Trust Centre for Human Genetics, University of Oxford
    Genetics of Complex Traits, University of Exeter Medical School, University of Exeter
    MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge
    King’s College London)

  • Xueling Sim

    (University of Michigan
    † Present addresses are provided in the Supplementary Information.)

  • Thomas W. Blackwell

    (University of Michigan)

  • Neil R. Robertson

    (Wellcome Trust Centre for Human Genetics, University of Oxford
    Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford)

  • N. William Rayner

    (Wellcome Trust Centre for Human Genetics, University of Oxford
    Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford
    Wellcome Trust Sanger Institute)

  • Pablo Cingolani

    (School of Computer Science, McGill University
    McGill University and Génome Québec Innovation Centre)

  • Adam E. Locke

    (University of Michigan
    † Present addresses are provided in the Supplementary Information.)

  • Juan Fernandez Tajes

    (Wellcome Trust Centre for Human Genetics, University of Oxford)

  • Heather M. Highland

    (Human Genetics Center, The University of Texas Graduate School of Biomedical Sciences at Houston, The University of Texas Health Science Center at Houston
    † Present addresses are provided in the Supplementary Information.)

  • Josee Dupuis

    (Boston University School of Public Health
    National Heart, Lung, and Blood Institute's Framingham Heart Study)

  • Peter S. Chines

    (Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health)

  • Cecilia M. Lindgren

    (Program in Medical and Population Genetics, Broad Institute
    Wellcome Trust Centre for Human Genetics, University of Oxford
    † Present addresses are provided in the Supplementary Information.)

  • Christopher Hartl

    (Program in Medical and Population Genetics, Broad Institute)

  • Anne U. Jackson

    (University of Michigan)

  • Han Chen

    (Boston University School of Public Health
    Harvard School of Public Health)

  • Jeroen R. Huyghe

    (University of Michigan
    † Present addresses are provided in the Supplementary Information.)

  • Martijn van de Bunt

    (Wellcome Trust Centre for Human Genetics, University of Oxford
    Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford)

  • Richard D. Pearson

    (Wellcome Trust Centre for Human Genetics, University of Oxford)

  • Ashish Kumar

    (Wellcome Trust Centre for Human Genetics, University of Oxford
    Chronic Disease Epidemiology, Swiss Tropical and Public Health Institute, University of Basel)

  • Martina Müller-Nurasyid

    (Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health
    University Hospital Grosshadern, Ludwig-Maximilians-Universität
    Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität
    DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance)

  • Niels Grarup

    (The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen)

  • Heather M. Stringham

    (University of Michigan)

  • Eric R. Gamazon

    (Section of Genetic Medicine, The University of Chicago
    † Present addresses are provided in the Supplementary Information.)

  • Jaehoon Lee

    (Seoul National University)

  • Yuhui Chen

    (Wellcome Trust Centre for Human Genetics, University of Oxford)

  • Robert A. Scott

    (MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge)

  • Jennifer E. Below

    (Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston)

  • Peng Chen

    (Saw Swee Hock School of Public Health, National University of Singapore, National University Health System)

  • Jinyan Huang

    (Harvard School of Public Health
    † Present addresses are provided in the Supplementary Information.)

  • Min Jin Go

    (Center for Genome Science, Korea National Institute of Health)

  • Michael L. Stitzel

    (The Jackson Laboratory for Genomic Medicine)

  • Dorota Pasko

    (Genetics of Complex Traits, University of Exeter Medical School, University of Exeter)

  • Stephen C. J. Parker

    (University of Michigan)

  • Tibor V. Varga

    (Lund University Diabetes Centre, Genetic and Molecular Epidemiology Unit, Lund University)

  • Todd Green

    (Program in Medical and Population Genetics, Broad Institute)

  • Nicola L. Beer

    (Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford)

  • Aaron G. Day-Williams

    (Wellcome Trust Sanger Institute
    † Present addresses are provided in the Supplementary Information.)

  • Teresa Ferreira

    (Wellcome Trust Centre for Human Genetics, University of Oxford)

  • Tasha Fingerlin

    (Colorado School of Public Health, University of Colorado)

  • Momoko Horikoshi

    (Wellcome Trust Centre for Human Genetics, University of Oxford
    Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford)

  • Cheng Hu

    (Shanghai Diabetes Institute, Shanghai Jiao Tong University Affiliated Sixth People's Hospital)

  • Iksoo Huh

    (Seoul National University)

  • Mohammad Kamran Ikram

    (Singapore Eye Research Institute, Singapore National Eye Centre
    Yong Loo Lin School of Medicine, National University of Singapore, National University Health System
    The Eye Academic Clinical Programme, Duke-NUS Graduate Medical School)

  • Bong-Jo Kim

    (Center for Genome Science, Korea National Institute of Health)

  • Yongkang Kim

    (Seoul National University)

  • Young Jin Kim

    (Center for Genome Science, Korea National Institute of Health)

  • Min-Seok Kwon

    (Interdisciplinary Program in Bioinformatics, Seoul National University)

  • Juyoung Lee

    (Center for Genome Science, Korea National Institute of Health)

  • Selyeong Lee

    (Seoul National University)

  • Keng-Han Lin

    (University of Michigan)

  • Taylor J. Maxwell

    (Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston
    † Present addresses are provided in the Supplementary Information.)

  • Yoshihiko Nagai

    (McGill University and Génome Québec Innovation Centre
    McGill University
    Research Institute of the McGill University Health Centre)

  • Xu Wang

    (Saw Swee Hock School of Public Health, National University of Singapore, National University Health System)

  • Ryan P. Welch

    (University of Michigan)

  • Joon Yoon

    (Interdisciplinary Program in Bioinformatics, Seoul National University)

  • Weihua Zhang

    (Imperial College London
    Ealing Hospital NHS Trust)

  • Nir Barzilai

    (Albert Einstein College of Medicine)

  • Benjamin F. Voight

    (University of Pennsylvania - Perelman School of Medicine
    University of Pennsylvania - Perelman School of Medicine, Philadelphia)

  • Bok-Ghee Han

    (Center for Genome Science, Korea National Institute of Health)

  • Christopher P. Jenkinson

    (University of Texas Health Science Center
    Research, South Texas Veterans Health Care System)

  • Teemu Kuulasmaa

    (Faculty of Health Sciences, Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland)

  • Johanna Kuusisto

    (Faculty of Health Sciences, Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland
    Kuopio University Hospital)

  • Alisa Manning

    (Program in Medical and Population Genetics, Broad Institute)

  • Maggie C. Y. Ng

    (Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine
    Center for Diabetes Research, Wake Forest School of Medicine)

  • Nicholette D. Palmer

    (Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine
    Center for Diabetes Research, Wake Forest School of Medicine
    Wake Forest School of Medicine)

  • Beverley Balkau

    (Centre for Research in Epidemiology and Population Health)

  • Alena Stančáková

    (Faculty of Health Sciences, Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland)

  • Hanna E. Abboud

    (University of Texas Health Science Center)

  • Heiner Boeing

    (German Institute of Human Nutrition Potsdam-Rehbruecke)

  • Vilmantas Giedraitis

    (Geriatrics, Uppsala University)

  • Dorairaj Prabhakaran

    (Centre for Chronic Disease Control)

  • Omri Gottesman

    (The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai)

  • James Scott

    (National Heart and Lung Institute, Cardiovascular Sciences, Hammersmith Campus, Imperial College London)

  • Jason Carey

    (Program in Medical and Population Genetics, Broad Institute)

  • Phoenix Kwan

    (University of Michigan)

  • George Grant

    (Program in Medical and Population Genetics, Broad Institute)

  • Joshua D. Smith

    (University of Washington School of Medicine)

  • Benjamin M. Neale

    (Program in Medical and Population Genetics, Broad Institute
    Analytic and Translational Genetics Unit, Massachusetts General Hospital
    Center for Human Genetic Research, Massachusetts General Hospital)

  • Shaun Purcell

    (Program in Medical and Population Genetics, Broad Institute
    Center for Human Genetic Research, Massachusetts General Hospital
    Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai)

  • Adam S. Butterworth

    (University of Cambridge)

  • Joanna M. M. Howson

    (University of Cambridge)

  • Heung Man Lee

    (The Chinese University of Hong Kong)

  • Yingchang Lu

    (The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai)

  • Soo-Heon Kwak

    (Seoul National University College of Medicine)

  • Wei Zhao

    (University of Pennsylvania)

  • John Danesh

    (Wellcome Trust Sanger Institute
    University of Cambridge
    NIHR Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge)

  • Vincent K. L. Lam

    (The Chinese University of Hong Kong)

  • Kyong Soo Park

    (Seoul National University College of Medicine
    Graduate School of Convergence Science and Technology, and College of Medicine, Seoul National University)

  • Danish Saleheen

    (University of Pennsylvania
    Center for Non-Communicable Diseases)

  • Wing Yee So

    (The Chinese University of Hong Kong)

  • Claudia H. T. Tam

    (The Chinese University of Hong Kong)

  • Uzma Afzal

    (Imperial College London)

  • David Aguilar

    (Baylor College of Medicine)

  • Rector Arya

    (University of Texas Health Science Center
    † Present addresses are provided in the Supplementary Information.)

  • Tin Aung

    (Singapore Eye Research Institute, Singapore National Eye Centre
    Yong Loo Lin School of Medicine, National University of Singapore, National University Health System
    The Eye Academic Clinical Programme, Duke-NUS Graduate Medical School)

  • Edmund Chan

    (Yong Loo Lin School of Medicine, National University of Singapore, National University Health System)

  • Carmen Navarro

    (Murcia Regional Health Council, IMIB-Arrixaca
    CIBER Epidemiología y Salud Pública (CIBERESP), Universidad de Murcia
    Unit of Preventive Medicine and Public Health, School of Medicine, University of Murcia)

  • Ching-Yu Cheng

    (Saw Swee Hock School of Public Health, National University of Singapore, National University Health System
    Singapore Eye Research Institute, Singapore National Eye Centre
    Yong Loo Lin School of Medicine, National University of Singapore, National University Health System
    The Eye Academic Clinical Programme, Duke-NUS Graduate Medical School)

  • Domenico Palli

    (Cancer Research and Prevention Institute (ISPO))

  • Adolfo Correa

    (University of Mississippi Medical Center)

  • Joanne E. Curran

    (South Texas Diabetes and Obesity Institute, Regional Academic Health Center, University of Texas Rio Grande Valley)

  • Denis Rybin

    (Boston University School of Public Health)

  • Vidya S. Farook

    (Texas Biomedical Research Institute)

  • Sharon P. Fowler

    (University of Texas Health Science Center)

  • Barry I. Freedman

    (Section on Nephrology, Wake Forest School of Medicine)

  • Michael Griswold

    (Center of Biostatistics and Bioinformatics, University of Mississippi Medical Center)

  • Daniel Esten Hale

    (University of Texas Health Science Center)

  • Pamela J. Hicks

    (Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine
    Center for Diabetes Research, Wake Forest School of Medicine
    Wake Forest School of Medicine)

  • Chiea-Chuen Khor

    (Saw Swee Hock School of Public Health, National University of Singapore, National University Health System
    Singapore Eye Research Institute, Singapore National Eye Centre
    Yong Loo Lin School of Medicine, National University of Singapore, National University Health System
    Yong Loo Lin School of Medicine, National University of Singapore, National University Health System)

  • Satish Kumar

    (South Texas Diabetes and Obesity Institute, Regional Academic Health Center, University of Texas Rio Grande Valley)

  • Benjamin Lehne

    (Imperial College London)

  • Dorothée Thuillier

    (CNRS-UMR8199, Lille University, Lille Pasteur Institute)

  • Wei Yen Lim

    (Saw Swee Hock School of Public Health, National University of Singapore, National University Health System)

  • Jianjun Liu

    (Saw Swee Hock School of Public Health, National University of Singapore, National University Health System
    Genome Institute of Singapore, A*STAR)

  • Yvonne T. van der Schouw

    (Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht)

  • Marie Loh

    (Imperial College London
    Institute of Health Sciences, University of Oulu
    Translational Laboratory in Genetic Medicine (TLGM), Agency for Science, Technology and Research (A*STAR)
    † Present addresses are provided in the Supplementary Information.)

  • Solomon K. Musani

    (Jackson Heart Study, University of Mississippi Medical Center)

  • Sobha Puppala

    (Texas Biomedical Research Institute)

  • William R. Scott

    (Imperial College London)

  • Loïc Yengo

    (CNRS-UMR8199, Lille University, Lille Pasteur Institute)

  • Sian-Tsung Tan

    (Ealing Hospital NHS Trust
    National Heart and Lung Institute, Cardiovascular Sciences, Hammersmith Campus, Imperial College London)

  • Herman A. Taylor Jr.

    (University of Mississippi Medical Center)

  • Farook Thameem

    (University of Texas Health Science Center
    † Present addresses are provided in the Supplementary Information.)

  • Gregory Wilson

    (College of Public Services, Jackson State University)

  • Tien Yin Wong

    (Singapore Eye Research Institute, Singapore National Eye Centre
    Yong Loo Lin School of Medicine, National University of Singapore, National University Health System
    The Eye Academic Clinical Programme, Duke-NUS Graduate Medical School)

  • Pål Rasmus Njølstad

    (KG Jebsen Center for Diabetes Research, University of Bergen
    Haukeland University Hospital)

  • Jonathan C. Levy

    (Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford)

  • Massimo Mangino

    (King’s College London)

  • Lori L. Bonnycastle

    (Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health)

  • Thomas Schwarzmayr

    (Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health)

  • João Fadista

    (Diabetes and Endocrinology, Lund University Diabetes Centre)

  • Gabriela L. Surdulescu

    (King’s College London)

  • Christian Herder

    (Institute of Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University
    German Center for Diabetes Research (DZD))

  • Christopher J. Groves

    (Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford)

  • Thomas Wieland

    (Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health)

  • Jette Bork-Jensen

    (The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen)

  • Ivan Brandslund

    (Institute of Regional Health Research, University of Southern Denmark
    Vejle Hospital)

  • Cramer Christensen

    (Vejle Hospital)

  • Heikki A. Koistinen

    (National Institute for Health and Welfare
    Abdominal Center: Endocrinology, University of Helsinki and Helsinki University Central Hospital
    Minerva Foundation Institute for Medical Research
    University of Helsinki and Helsinki University Central Hospital)

  • Alex S. F. Doney

    (Medical Research Institute, Ninewells Hospital and Medical School)

  • Leena Kinnunen

    (National Institute for Health and Welfare)

  • Tõnu Esko

    (Program in Medical and Population Genetics, Broad Institute
    Estonian Genome Center, University of Tartu
    Harvard Medical School
    Boston Children's Hospital)

  • Andrew J. Farmer

    (University of Oxford)

  • Liisa Hakaste

    (Abdominal Center: Endocrinology, University of Helsinki and Helsinki University Central Hospital
    Folkhälsan Research Centre
    Research Programs Unit, Diabetes and Obesity, University of Helsinki)

  • Dylan Hodgkiss

    (King’s College London)

  • Jasmina Kravic

    (Diabetes and Endocrinology, Lund University Diabetes Centre)

  • Valeriya Lyssenko

    (Diabetes and Endocrinology, Lund University Diabetes Centre)

  • Mette Hollensted

    (The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen)

  • Marit E. Jørgensen

    (Steno Diabetes Center)

  • Torben Jørgensen

    (Research Centre for Prevention and Health, Capital Region of Denmark
    Institute of Health Sciences, University of Copenhagen
    Faculty of Medicine, Aalborg University)

  • Claes Ladenvall

    (Diabetes and Endocrinology, Lund University Diabetes Centre
    † Present addresses are provided in the Supplementary Information.)

  • Johanne Marie Justesen

    (The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen)

  • Annemari Käräjämäki

    (Vaasa Central Hospital
    Diabetes Center, Vaasa Health Care Center)

  • Jennifer Kriebel

    (German Center for Diabetes Research (DZD)
    Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health
    Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health)

  • Wolfgang Rathmann

    (Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University)

  • Lars Lannfelt

    (Geriatrics, Uppsala University)

  • Torsten Lauritzen

    (Section of General Practice, Aarhus University)

  • Narisu Narisu

    (Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health)

  • Allan Linneberg

    (Research Centre for Prevention and Health, Capital Region of Denmark
    Department of Clinical Experimental Research
    Faculty of Health and Medical Sciences, University of Copenhagen)

  • Olle Melander

    (Hypertension and Cardiovascular Disease, Lund University)

  • Lili Milani

    (Estonian Genome Center, University of Tartu)

  • Matt Neville

    (Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford
    Oxford NIHR Biomedical Research Centre, Oxford University Hospitals Trust)

  • Marju Orho-Melander

    (Diabetes and Cardiovascular Disease, Genetic Epidemiology, Lund University)

  • Lu Qi

    (Harvard School of Public Health
    Brigham and Women’s Hospital and Harvard Medical School
    † Present addresses are provided in the Supplementary Information.)

  • Qibin Qi

    (Harvard School of Public Health
    Albert Einstein College of Medicine)

  • Michael Roden

    (Institute of Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University
    German Center for Diabetes Research (DZD)
    Medical Faculty, Heinrich-Heine University)

  • Olov Rolandsson

    (Umeå University)

  • Amy Swift

    (Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health)

  • Anders H. Rosengren

    (Diabetes and Endocrinology, Lund University Diabetes Centre)

  • Kathleen Stirrups

    (Wellcome Trust Sanger Institute
    † Present addresses are provided in the Supplementary Information.)

  • Andrew R. Wood

    (Genetics of Complex Traits, University of Exeter Medical School, University of Exeter)

  • Evelin Mihailov

    (Estonian Genome Center, University of Tartu)

  • Christine Blancher

    (High Throughput Genomics, Oxford Genomics Centre, Wellcome Trust Centre for Human Genetics, University of Oxford)

  • Mauricio O. Carneiro

    (Program in Medical and Population Genetics, Broad Institute)

  • Jared Maguire

    (Program in Medical and Population Genetics, Broad Institute)

  • Ryan Poplin

    (Program in Medical and Population Genetics, Broad Institute)

  • Khalid Shakir

    (Program in Medical and Population Genetics, Broad Institute)

  • Timothy Fennell

    (Program in Medical and Population Genetics, Broad Institute)

  • Mark DePristo

    (Program in Medical and Population Genetics, Broad Institute
    † Present addresses are provided in the Supplementary Information.)

  • Martin Hrabé de Angelis

    (German Center for Diabetes Research (DZD)
    Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health
    Center of Life and Food Sciences Weihenstephan, Technische Universität München)

  • Panos Deloukas

    (William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London
    Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University)

  • Anette P. Gjesing

    (The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen)

  • Goo Jun

    (University of Michigan
    Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston)

  • Peter Nilsson

    (Medicine, Lund University)

  • Jacquelyn Murphy

    (Program in Medical and Population Genetics, Broad Institute)

  • Robert Onofrio

    (Program in Medical and Population Genetics, Broad Institute)

  • Barbara Thorand

    (German Center for Diabetes Research (DZD)
    Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health)

  • Torben Hansen

    (The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen
    Faculty of Health Sciences, University of Southern Denmark)

  • Christa Meisinger

    (German Center for Diabetes Research (DZD)
    Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health)

  • Frank B. Hu

    (Harvard School of Public Health
    Harvard School of Public Health)

  • Bo Isomaa

    (Folkhälsan Research Centre
    Department of Social Services and Health Care)

  • Fredrik Karpe

    (Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford
    Oxford NIHR Biomedical Research Centre, Oxford University Hospitals Trust)

  • Liming Liang

    (Harvard School of Public Health
    Harvard School of Public Health)

  • Annette Peters

    (DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance
    German Center for Diabetes Research (DZD)
    Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health)

  • Cornelia Huth

    (German Center for Diabetes Research (DZD)
    Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health)

  • Stephen P. O’Rahilly

    (Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge)

  • Colin N. A. Palmer

    (Pat Macpherson Centre for Pharmacogenetics and Pharmacogenomics, Ninewells Hospital and Medical School, University of Dundee)

  • Oluf Pedersen

    (The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen)

  • Rainer Rauramaa

    (Foundation for Research in Health, Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine)

  • Jaakko Tuomilehto

    (National Institute for Health and Welfare
    Center for Vascular Prevention, Danube University Krems
    Diabetes Research Group, King Abdulaziz University
    Instituto de Investigacion Sanitaria del Hospital Universario LaPaz (IdiPAZ), University Hospital LaPaz, Autonomous University of Madrid)

  • Veikko Salomaa

    (National Institute for Health and Welfare)

  • Richard M. Watanabe

    (Keck School of Medicine, University of Southern California
    Keck School of Medicine, University of Southern California
    Diabetes and Obesity Research Institute, Keck School of Medicine, University of Southern California)

  • Ann-Christine Syvänen

    (Molecular Medicine and Science for Life Laboratory, Uppsala University)

  • Richard N. Bergman

    (Cedars-Sinai Diabetes and Obesity Research Institute)

  • Dwaipayan Bharadwaj

    (Functional Genomics Unit, CSIR-Institute of Genomics & Integrative Biology (CSIR-IGIB)
    † Present addresses are provided in the Supplementary Information.)

  • Erwin P. Bottinger

    (The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai)

  • Yoon Shin Cho

    (Hallym University)

  • Giriraj R. Chandak

    (CSIR-Centre for Cellular and Molecular Biology
    † Present addresses are provided in the Supplementary Information.)

  • Juliana C. N. Chan

    (The Chinese University of Hong Kong
    Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong
    Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong)

  • Kee Seng Chia

    (Saw Swee Hock School of Public Health, National University of Singapore, National University Health System)

  • Mark J. Daly

    (Analytic and Translational Genetics Unit, Massachusetts General Hospital)

  • Shah B. Ebrahim

    (Centre for Chronic Disease Control)

  • Claudia Langenberg

    (MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge)

  • Paul Elliott

    (Imperial College London
    MRC-PHE Centre for Environment and Health, Imperial College London)

  • Kathleen A. Jablonski

    (The Biostatistics Center, The George Washington University)

  • Donna M. Lehman

    (University of Texas Health Science Center)

  • Weiping Jia

    (Shanghai Diabetes Institute, Shanghai Jiao Tong University Affiliated Sixth People's Hospital)

  • Ronald C. W. Ma

    (The Chinese University of Hong Kong
    Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong
    Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong)

  • Toni I. Pollin

    (Diabetes and Nutrition, and Program in Personalized and Genomic Medicine, University of Maryland School of Medicine)

  • Manjinder Sandhu

    (Wellcome Trust Sanger Institute
    University of Cambridge)

  • Nikhil Tandon

    (All India Institute of Medical Sciences)

  • Philippe Froguel

    (CNRS-UMR8199, Lille University, Lille Pasteur Institute
    School of Public Health, Imperial College London)

  • Inês Barroso

    (Wellcome Trust Sanger Institute
    Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge)

  • Yik Ying Teo

    (Saw Swee Hock School of Public Health, National University of Singapore, National University Health System
    Life Sciences Institute, National University of Singapore
    National University of Singapore)

  • Eleftheria Zeggini

    (Wellcome Trust Sanger Institute)

  • Ruth J. F. Loos

    (The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai)

  • Kerrin S. Small

    (King’s College London)

  • Janina S. Ried

    (Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health)

  • Ralph A. DeFronzo

    (University of Texas Health Science Center)

  • Harald Grallert

    (German Center for Diabetes Research (DZD)
    Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health
    Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health)

  • Benjamin Glaser

    (Endocrinology and Metabolism Service, Hadassah-Hebrew University Medical Center)

  • Andres Metspalu

    (Estonian Genome Center, University of Tartu)

  • Nicholas J. Wareham

    (MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge)

  • Mark Walker

    (The Medical School, Institute of Cellular Medicine, Newcastle University)

  • Eric Banks

    (Program in Medical and Population Genetics, Broad Institute)

  • Christian Gieger

    (Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health
    Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health
    Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health)

  • Erik Ingelsson

    (Wellcome Trust Centre for Human Genetics, University of Oxford
    Molecular Epidemiology and Science for Life Laboratory, Uppsala University
    † Present addresses are provided in the Supplementary Information.)

  • Hae Kyung Im

    (Section of Genetic Medicine, The University of Chicago)

  • Thomas Illig

    (Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health
    Hannover Unified Biobank, Hannover Medical School
    Institute for Human Genetics, Hannover Medical School)

  • Paul W. Franks

    (Lund University Diabetes Centre, Genetic and Molecular Epidemiology Unit, Lund University
    Harvard School of Public Health
    Umeå University)

  • Gemma Buck

    (High Throughput Genomics, Oxford Genomics Centre, Wellcome Trust Centre for Human Genetics, University of Oxford)

  • Joseph Trakalo

    (High Throughput Genomics, Oxford Genomics Centre, Wellcome Trust Centre for Human Genetics, University of Oxford)

  • David Buck

    (High Throughput Genomics, Oxford Genomics Centre, Wellcome Trust Centre for Human Genetics, University of Oxford)

  • Inga Prokopenko

    (Wellcome Trust Centre for Human Genetics, University of Oxford
    Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford
    School of Public Health, Imperial College London)

  • Reedik Mägi

    (Estonian Genome Center, University of Tartu)

  • Lars Lind

    (Uppsala University)

  • Yossi Farjoun

    (Data Sciences and Data Engineering, Broad Institute)

  • Katharine R. Owen

    (Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford
    Oxford NIHR Biomedical Research Centre, Oxford University Hospitals Trust)

  • Anna L. Gloyn

    (Wellcome Trust Centre for Human Genetics, University of Oxford
    Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford
    Oxford NIHR Biomedical Research Centre, Oxford University Hospitals Trust)

  • Konstantin Strauch

    (Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health
    Institute of Medical Informatics, Biometry and Epidemiology, Chair of Genetic Epidemiology, Ludwig-Maximilians-Universität)

  • Tiinamaija Tuomi

    (Abdominal Center: Endocrinology, University of Helsinki and Helsinki University Central Hospital
    Folkhälsan Research Centre
    Research Programs Unit, Diabetes and Obesity, University of Helsinki
    Institute for Molecular Medicine Finland (FIMM), University of Helsinki)

  • Jaspal Singh Kooner

    (Ealing Hospital NHS Trust
    National Heart and Lung Institute, Cardiovascular Sciences, Hammersmith Campus, Imperial College London
    Imperial College Healthcare NHS Trust, Imperial College London)

  • Jong-Young Lee

    (Center for Genome Science, Korea National Institute of Health
    † Present addresses are provided in the Supplementary Information.)

  • Taesung Park

    (Seoul National University
    Interdisciplinary Program in Bioinformatics, Seoul National University)

  • Peter Donnelly

    (Wellcome Trust Centre for Human Genetics, University of Oxford
    University of Oxford)

  • Andrew D. Morris

    (Clinical Research Centre, Centre for Molecular Medicine, Ninewells Hospital and Medical School
    The Usher Institute to the Population Health Sciences and Informatics, University of Edinburgh)

  • Andrew T. Hattersley

    (University of Exeter Medical School, University of Exeter)

  • Donald W. Bowden

    (Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine
    Center for Diabetes Research, Wake Forest School of Medicine
    Wake Forest School of Medicine)

  • Francis S. Collins

    (Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health)

  • Gil Atzmon

    (Albert Einstein College of Medicine
    University of Haifa)

  • John C. Chambers

    (Imperial College London
    Ealing Hospital NHS Trust
    Imperial College Healthcare NHS Trust, Imperial College London)

  • Timothy D. Spector

    (King’s College London)

  • Markku Laakso

    (Faculty of Health Sciences, Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland
    Kuopio University Hospital)

  • Tim M. Strom

    (Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health
    Institute of Human Genetics, Technische Universität München)

  • Graeme I. Bell

    (The University of Chicago)

  • John Blangero

    (South Texas Diabetes and Obesity Institute, Regional Academic Health Center, University of Texas Rio Grande Valley)

  • Ravindranath Duggirala

    (Texas Biomedical Research Institute)

  • E. Shyong Tai

    (Saw Swee Hock School of Public Health, National University of Singapore, National University Health System
    Yong Loo Lin School of Medicine, National University of Singapore, National University Health System
    Cardiovascular & Metabolic Disorders Program, Duke-NUS Medical School Singapore)

  • Gilean McVean

    (Wellcome Trust Centre for Human Genetics, University of Oxford
    Li Ka Shing Centre for Health Information and Discovery, University of Oxford)

  • Craig L. Hanis

    (Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston)

  • James G. Wilson

    (University of Mississippi Medical Center)

  • Mark Seielstad

    (University of California, San Francisco
    Blood Systems Research Institute)

  • Timothy M. Frayling

    (Genetics of Complex Traits, University of Exeter Medical School, University of Exeter)

  • James B. Meigs

    (Harvard Medical School)

  • Nancy J. Cox

    (Section of Genetic Medicine, The University of Chicago
    † Present addresses are provided in the Supplementary Information.)

  • Rob Sladek

    (McGill University and Génome Québec Innovation Centre
    McGill University
    McGill University)

  • Eric S. Lander

    (Broad Institute of MIT and Harvard)

  • Stacey Gabriel

    (Program in Medical and Population Genetics, Broad Institute)

  • Noël P. Burtt

    (Program in Medical and Population Genetics, Broad Institute)

  • Karen L. Mohlke

    (University of North Carolina)

  • Thomas Meitinger

    (Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health
    Institute of Human Genetics, Technische Universität München)

  • Leif Groop

    (Diabetes and Endocrinology, Lund University Diabetes Centre
    Institute for Molecular Medicine Finland (FIMM), University of Helsinki)

  • Goncalo Abecasis

    (University of Michigan)

  • Jose C. Florez

    (Program in Medical and Population Genetics, Broad Institute
    Center for Human Genetic Research, Massachusetts General Hospital
    Harvard Medical School
    Diabetes Research Center (Diabetes Unit), Massachusetts General Hospital)

  • Laura J. Scott

    (University of Michigan)

  • Andrew P. Morris

    (Wellcome Trust Centre for Human Genetics, University of Oxford
    Estonian Genome Center, University of Tartu
    University of Liverpool)

  • Hyun Min Kang

    (University of Michigan)

  • Michael Boehnke

    (University of Michigan)

  • David Altshuler

    (Program in Medical and Population Genetics, Broad Institute
    Massachusetts General Hospital
    Harvard Medical School
    Harvard Medical School)

  • Mark I. McCarthy

    (Wellcome Trust Centre for Human Genetics, University of Oxford
    Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford
    Oxford NIHR Biomedical Research Centre, Oxford University Hospitals Trust)

Abstract

The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.

Suggested Citation

  • Christian Fuchsberger & Jason Flannick & Tanya M. Teslovich & Anubha Mahajan & Vineeta Agarwala & Kyle J. Gaulton & Clement Ma & Pierre Fontanillas & Loukas Moutsianas & Davis J. McCarthy & Manuel A. , 2016. "The genetic architecture of type 2 diabetes," Nature, Nature, vol. 536(7614), pages 41-47, August.
    • Handle: RePEc:nat:nature:v:536:y:2016:i:7614:d:10.1038_nature18642
    DOI: 10.1038/nature18642
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/nature18642
    File Function: Abstract
    Download Restriction: Access to the full text of the articles in this series is restricted.
    File URL: https://libkey.io/10.1038/nature18642?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    As the access to this document is restricted, you may want to search for a different version of it.

    Citations

    Citations are extracted by the CitEc Project, subscribe to its RSS feed for this item.
    as


    Cited by:

    1. Young Jin Kim & Sanghoon Moon & Mi Yeong Hwang & Sohee Han & Hye-Mi Jang & Jinhwa Kong & Dong Mun Shin & Kyungheon Yoon & Sung Min Kim & Jong-Eun Lee & Anubha Mahajan & Hyun-Young Park & Mark I. McCar, 2022. "The contribution of common and rare genetic variants to variation in metabolic traits in 288,137 East Asians," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    2. Nikola Szweda-Gandor & Mirosław Śnit & Władysław Grzeszczak, 2021. "Association between Selected Polymorphisms rs12086634, rs846910, rs4844880, rs3753519 of 11β-Hydroxysteroid Dehydrogenase Type 1 ( HSD11B1 ) and the Presence of Insulin Resistance in the Polish Popula," IJERPH, MDPI, vol. 18(19), pages 1-9, September.
    3. Dixon, Padraig & Harrison, Sean & Hollingworth, William & Davies, Neil M. & Davey Smith, George, 2022. "Estimating the causal effect of liability to disease on healthcare costs using Mendelian Randomization," Economics & Human Biology, Elsevier, vol. 46(C).
    4. Donghua Hu & Min Tan & Dongliang Lu & Brian Kleiboeker & Xuejing Liu & Hongsuk Park & Alexxai V. Kravitz & Kooresh I. Shoghi & Yu-Hua Tseng & Babak Razani & Akihiro Ikeda & Irfan J. Lodhi, 2023. "TMEM135 links peroxisomes to the regulation of brown fat mitochondrial fission and energy homeostasis," Nature Communications, Nature, vol. 14(1), pages 1-20, December.
    5. Aimee M. Deaton & Aditi Dubey & Lucas D. Ward & Peter Dornbos & Jason Flannick & Elaine Yee & Simina Ticau & Leila Noetzli & Margaret M. Parker & Rachel A. Hoffing & Carissa Willis & Mollie E. Plekan , 2022. "Rare loss of function variants in the hepatokine gene INHBE protect from abdominal obesity," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    6. Hwee Hui Lau & Nicole A. J. Krentz & Fernando Abaitua & Marta Perez-Alcantara & Jun-Wei Chan & Jila Ajeian & Soumita Ghosh & Yunkyeong Lee & Jing Yang & Swaraj Thaman & Benoite Champon & Han Sun & Alo, 2023. "PAX4 loss of function increases diabetes risk by altering human pancreatic endocrine cell development," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    7. Oriol Juanola & Sebastián Martínez-López & Rubén Francés & Isabel Gómez-Hurtado, 2021. "Non-Alcoholic Fatty Liver Disease: Metabolic, Genetic, Epigenetic and Environmental Risk Factors," IJERPH, MDPI, vol. 18(10), pages 1-24, May.
    8. Ting Fu & Kofi Amoah & Tracey W. Chan & Jae Hoon Bahn & Jae-Hyung Lee & Sari Terrazas & Rockie Chong & Sriram Kosuri & Xinshu Xiao, 2024. "Massively parallel screen uncovers many rare 3′ UTR variants regulating mRNA abundance of cancer driver genes," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    9. Xianyong Yin & Lap Sum Chan & Debraj Bose & Anne U. Jackson & Peter VandeHaar & Adam E. Locke & Christian Fuchsberger & Heather M. Stringham & Ryan Welch & Ketian Yu & Lilian Fernandes Silva & Susan K, 2022. "Genome-wide association studies of metabolites in Finnish men identify disease-relevant loci," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    10. Niels Berg & Mar Rodríguez-Girondo & Ingrid K. Dijk & P. Eline Slagboom & Marian Beekman, 2023. "Increasing number of long-lived ancestors marks a decade of healthspan extension and healthier metabolomics profiles," Nature Communications, Nature, vol. 14(1), pages 1-13, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:nature:v:536:y:2016:i:7614:d:10.1038_nature18642. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    We have no bibliographic references for this item. You can help adding them by using this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.