Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
Jason Flannick 1 2, Christian Fuchsberger 3, Anubha Mahajan 4, Tanya M Teslovich 3, Vineeta Agarwala 2 5, Kyle J Gaulton 4, Lizz Caulkins 2, Ryan Koesterer 2, Clement Ma 3, Loukas Moutsianas 4, Davis J McCarthy 4 6, Manuel A Rivas 4, John R B Perry 4 7 8 9, Xueling Sim 3, Thomas W Blackwell 3, Neil R Robertson 4 10, N William Rayner 4 10 11, Pablo Cingolani 12 13, Adam E Locke 3, Juan Fernandez Tajes 4, Heather M Highland 14, Josee Dupuis 15 16, Peter S Chines 17, Cecilia M Lindgren 2 4, Christopher Hartl 2, Anne U Jackson 3, Han Chen 15 18, Jeroen R Huyghe 3, Martijn van de Bunt 4 10, Richard D Pearson 4, Ashish Kumar 4 19, Martina Müller-Nurasyid 20 21 22 23, Niels Grarup 24, Heather M Stringham 3, Eric R Gamazon 25, Jaehoon Lee 26, Yuhui Chen 4, Robert A Scott 8, Jennifer E Below 27, Peng Chen 28, Jinyan Huang 29, Min Jin Go 30, Michael L Stitzel 31, Dorota Pasko 7, Stephen C J Parker 32, Tibor V Varga 33, Todd Green 2, Nicola L Beer 10, Aaron G Day-Williams 11, Teresa Ferreira 4, Tasha Fingerlin 34, Momoko Horikoshi 4 10, Cheng Hu 35, Iksoo Huh 26, Mohammad Kamran Ikram 36 37 38, Bong-Jo Kim 30, Yongkang Kim 26, Young Jin Kim 30, Min-Seok Kwon 39, Juyoung Lee 30, Selyeong Lee 26, Keng-Han Lin 3, Taylor J Maxwell 27, Yoshihiko Nagai 13 40 41, Xu Wang 28, Ryan P Welch 3, Joon Yoon 39, Weihua Zhang 42 43, Nir Barzilai 44, Benjamin F Voight 45 46, Bok-Ghee Han 30, Christopher P Jenkinson 47 48, Teemu Kuulasmaa 49, Johanna Kuusisto 49 50, Alisa Manning 2, Maggie C Y Ng 51 52, Nicholette D Palmer 51 52 53, Beverley Balkau 54, Alena Stančáková 49, Hanna E Abboud 47, Heiner Boeing 55, Vilmantas Giedraitis 56, Dorairaj Prabhakaran 57, Omri Gottesman 58, James Scott 59, Jason Carey 2, Phoenix Kwan 3, George Grant 2, Joshua D Smith 60, Benjamin M Neale 2 61, Shaun Purcell 2 62 63, Adam S Butterworth 64, Joanna M M Howson 64, Heung Man Lee 65, Yingchang Lu 58, Soo-Heon Kwak 66, Wei Zhao 67, John Danesh 11 64 68, Vincent K L Lam 65, Kyong Soo Park 69, Danish Saleheen 70 71, Wing Yee So 65, Claudia H T Tam 65, Uzma Afzal 42, David Aguilar 72, Rector Arya 73, Tin Aung 36 37 38, Edmund Chan 74, Carmen Navarro 75 76 77, Ching-Yu Cheng 28 36 37 38, Domenico Palli 78, Adolfo Correa 79, Joanne E Curran 80, Dennis Rybin 15, Vidya S Farook 81, Sharon P Fowler 47, Barry I Freedman 82, Michael Griswold 83, Daniel Esten Hale 73, Pamela J Hicks 51 52 53, Chiea-Chuen Khor 28 36 37 84 85, Satish Kumar 80, Benjamin Lehne 42, Dorothée Thuillier 86, Wei Yen Lim 28, Jianjun Liu 28 85, Marie Loh 42 87 88, Solomon K Musani 89, Sobha Puppala 81, William R Scott 42, Loïc Yengo 86, Sian-Tsung Tan 43 59, Herman A Taylor 79, Farook Thameem 47, Gregory Wilson 90, Tien Yin Wong 36 37 38, Pål Rasmus Njølstad 91 92, Jonathan C Levy 10, Massimo Mangino 9 93, Lori L Bonnycastle 17, Thomas Schwarzmayr 94, João Fadista 95, Gabriela L Surdulescu 9, Christian Herder 96 97, Christopher J Groves 10, Thomas Wieland 94, Jette Bork-Jensen 24, Ivan Brandslund 98 99, Cramer Christensen 100, Heikki A Koistinen 101 102 103 104, Alex S F Doney 105, Leena Kinnunen 101, Tõnu Esko 2 106 107 108, Andrew J Farmer 109, Liisa Hakaste 102 110 111, Dylan Hodgkiss 9, Jasmina Kravic 95, Valeri Lyssenko 95, Mette Hollensted 24, Marit E Jørgensen 112, Torben Jørgensen 113 114 115, Claes Ladenvall 95, Johanne Marie Justesen 24, Annemari Käräjämäki 116 117, Jennifer Kriebel 97 118 119, Wolfgang Rathmann 97 120, Lars Lannfelt 56, Torsten Lauritzen 121, Narisu Narisu 17, Allan Linneberg 113 122 123, Olle Melander 124, Lili Milani 106, Matt Neville 10 125, Marju Orho-Melander 126, Lu Qi 127 128, Qibin Qi 127 129, Michael Roden 96 97 130, Olov Rolandsson 131, Amy Swift 17, Anders H Rosengren 95, Kathleen Stirrups 11, Andrew R Wood 7, Evelin Mihailov 106, Christine Blancher 132, Mauricio O Carneiro 2, Jared Maguire 2, Ryan Poplin 2, Khalid Shakir 2, Timothy Fennell 2, Mark DePristo 2, Martin Hrabé de Angelis 97 133 134, Panos Deloukas 11 135 136, Anette P Gjesing 24, Goo Jun 3 27, Peter Nilsson 137, Jacquelyn Murphy 2, Robert Onofrio 2, Barbara Thorand 97 118, Torben Hansen 24 138, Christa Meisinger 97 118, Frank B Hu 29 127, Bo Isomaa 110 139, Fredrik Karpe 10 125, Liming Liang 18 29, Annette Peters 23 97 118, Cornelia Huth 97 118, Stephen P O'Rahilly 140, Colin N A Palmer 141, Oluf Pedersen 24, Rainer Rauramaa 142, Jaakko Tuomilehto 143 144 145 146, Veikko Salomaa 146, Richard M Watanabe 147 148 149, Ann-Christine Syvänen 150, Richard N Bergman 151, Dwaipayan Bharadwaj 152, Erwin P Bottinger 58, Yoon Shin Cho 153, Giriraj R Chandak 154, Juliana Cn Chan 65 155 156, Kee Seng Chia 28, Mark J Daly 61, Shah B Ebrahim 57, Claudia Langenberg 8, Paul Elliott 42 157, Kathleen A Jablonski 158, Donna M Lehman 47, Weiping Jia 35, Ronald C W Ma 65 155 156, Toni I Pollin 159, Manjinder Sandhu 11 64, Nikhil Tandon 160, Philippe Froguel 86 161, Inês Barroso 11 140, Yik Ying Teo 28 162 163, Eleftheria Zeggini 11, Ruth J F Loos 58, Kerrin S Small 9, Janina S Ried 20, Ralph A DeFronzo 47, Harald Grallert 97 118 119, Benjamin Glaser 164, Andres Metspalu 106, Nicholas J Wareham 8, Mark Walker 165, Eric Banks 2, Christian Gieger 20 118 119, Erik Ingelsson 4 166, Hae Kyung Im 25, Thomas Illig 119 167 168, Paul W Franks 33 127 131, Gemma Buck 132, Joseph Trakalo 132, David Buck 132, Inga Prokopenko 4 10 161, Reedik Mägi 106, Lars Lind 169, Yossi Farjoun 170, Katharine R Owen 10 125, Anna L Gloyn 4 10 125, Konstantin Strauch 20 22, Tiinamaija Tuomi 102 110 111 171, Jaspal Singh Kooner 43 59 172, Jong-Young Lee 30, Taesung Park 26 39, Peter Donnelly 4 6, Andrew D Morris 173 174, Andrew T Hattersley 175, Donald W Bowden 51 52 53, Francis S Collins 17, Gil Atzmon 44 176, John C Chambers 42 43 172, Timothy D Spector 9, Markku Laakso 49 50, Tim M Strom 94 177, Graeme I Bell 178, John Blangero 80, Ravindranath Duggirala 81, E Shyong Tai 28 74 179, Gilean McVean 4 180, Craig L Hanis 27, James G Wilson 181, Mark Seielstad 182 183, Timothy M Frayling 7, James B Meigs 184, Nancy J Cox 25, Rob Sladek 13 40 185, Eric S Lander 186, Stacey Gabriel 2, Karen L Mohlke 187, Thomas Meitinger 94 177, Leif Groop 95 171, Goncalo Abecasis 3, Laura J Scott 3, Andrew P Morris 4 106 188, Hyun Min Kang 1, David Altshuler 1 2 107 189 190 191, Noël P Burtt 2, Jose C Florez 2 62 189 190, Michael Boehnke 3, Mark I McCarthy 4 10 125
Affiliations
Affiliations
- 1Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.
- 2Program in Medical and Population Genetics, Broad Institute, Cambridge, Massachusetts, USA.
- 3Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.
- 4Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
- 5Harvard-MIT Division of Health Sciences and Technology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
- 6Department of Statistics, University of Oxford, Oxford, UK.
- 7Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, UK.
- 8MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
- 9Department of Twin Research and Genetic Epidemiology, King's College London, London, UK.
- 10Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, UK.
- 11Department of Human Genetics, Wellcome Trust Sanger Institute, Hinxton, Cambridgeshire, UK.
- 12School of Computer Science, McGill University, Montreal, Quebec, Canada.
- 13McGill University and Génome Québec Innovation Centre, Montreal, Quebec, Canada.
- 14Human Genetics Center, The University of Texas Graduate School of Biomedical Sciences at Houston, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
- 15Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts, USA.
- 16National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA.
- 17Medical Genomics and Metabolic Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.
- 18Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA.
- 19Chronic Disease Epidemiology, Swiss Tropical and Public Health Institute, University of Basel, Basel, Switzerland.
- 20Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
- 21Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-Universität, Munich, Germany.
- 22Chair of Genetic Epidemiology, IBE, Faculty of Medicine, LMU Munich, Germany.
- 23DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, Munich, Germany.
- 24The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
- 25Department of Medicine, Section of Genetic Medicine, The University of Chicago, Chicago, Illinois, USA.
- 26Department of Statistics, Seoul National University, Seoul, Republic of Korea.
- 27Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, Texas, USA.
- 28Saw Swee Hock School of Public Health, National University of Singapore, National University Health System, Singapore, Singapore.
- 29Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
- 30Center for Genome Science, Korea National Institute of Health, Chungcheongbuk-do, Republic of Korea.
- 31The Jackson Laboratory for Genomic Medicine, Farmington, Connecticut, USA.
- 32Departments of Computational Medicine & Bioinformatics and Human Genetics, University of Michigan, Ann Arbor, Michigan, USA.
- 33Department of Clinical Sciences, Lund University Diabetes Centre, Genetic and Molecular Epidemiology Unit, Lund University, Malmö, Sweden.
- 34Department of Epidemiology, Colorado School of Public Health, University of Colorado, Aurora, Colorado, USA.
- 35Department of Endocrinology and Metabolism, Shanghai Diabetes Institute, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.
- 36Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
- 37Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore, Singapore.
- 38The Eye Academic Clinical Programme, Duke-NUS Graduate Medical School, Singapore, Singapore.
- 39Interdisciplinary Program in Bioinformatics, Seoul National University, Seoul, Republic of Korea.
- 40Department of Human Genetics, McGill University, Montreal, Quebec, Canada.
- 41Research Institute of the McGill University Health Centre, Montreal, Quebec, Canada.
- 42Department of Epidemiology and Biostatistics, Imperial College London, London, UK.
- 43Department of Cardiology, Ealing Hospital NHS Trust, Southall, Middlesex, UK.
- 44Departments of Medicine and Genetics, Albert Einstein College of Medicine, New York, USA.
- 45Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania-Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
- 46Department of Genetics, University of Pennsylvania-Perelman School of Medicine, Philadelphia, Pennsylvania, USA.
- 47Department of Medicine, University of Texas Health Science Center, San Antonio, Texas, USA.
- 48Research, South Texas Veterans Health Care System, San Antonio, Texas, USA.
- 49Faculty of Health Sciences, Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland.
- 50Kuopio University Hospital, Kuopio, Finland.
- 51Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
- 52Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
- 53Department of Biochemistry, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
- 54Centre for Research in Epidemiology and Population Health, Inserm U1018, Villejuif, France.
- 55German Institute of Human Nutrition Potsdam-Rehbruecke, Nuthetal, Germany.
- 56Department of Public Health and Caring Sciences, Geriatrics, Uppsala University, Uppsala, Sweden.
- 57Centre for Chronic Disease Control, New Delhi, India.
- 58The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai, New York, USA.
- 59National Heart and Lung Institute, Cardiovascular Sciences, Hammersmith Campus, Imperial College London, London, UK.
- 60Department of Genome Sciences, University of Washington School of Medicine, Seattle, Washington, USA.
- 61Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
- 62Center for Genomic Medicine, Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
- 63Department of Psychiatry, Icahn Institute for Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, New York, USA.
- 64Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
- 65Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China.
- 66Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
- 67Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
- 68NIHR Blood and Transplant Research Unit in Donor Health and Genomics, Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK.
- 69Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine, Seoul National University, Seoul, Republic of Korea.
- 70Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
- 71Center for Non-Communicable Diseases, Karachi, Pakistan.
- 72Cardiovascular Division, Baylor College of Medicine, Houston, Texas, USA.
- 73Department of Pediatrics, University of Texas Health Science Center, San Antonio, Texas, USA.
- 74Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore, Singapore.
- 75Department of Epidemiology, Murcia Regional Health Council, IMIB-Arrixaca, Murcia, Spain.
- 76CIBER Epidemiología y Salud Pública (CIBERESP), Spain.
- 77Unit of Preventive Medicine and Public Health, School of Medicine, University of Murcia, Spain.
- 78Cancer Research and Prevention Institute (ISPO), Florence, Italy.
- 79Department of Medicine, University of Mississippi Medical Center, Jackson, Mississippi, USA.
- 80South Texas Diabetes and Obesity Institute, Regional Academic Health Center, University of Texas Health Science Center at San Antonio/University of Texas Rio Grande Valley, Brownsville, Texas, USA.
- 81Department of Genetics, Texas Biomedical Research Institute, San Antonio, Texas, USA.
- 82Department of Internal Medicine, Section on Nephrology, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA.
- 83Center of Biostatistics and Bioinformatics, University of Mississippi Medical Center, Jackson, Mississippi, USA.
- 84Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore, Singapore.
- 85Division of Human Genetics, Genome Institute of Singapore, A*STAR, Singapore, Singapore.
- 86CNRS-UMR8199, Lille University, Lille Pasteur Institute, Lille, France.
- 87Institute of Health Sciences, University of Oulu, Oulu, Finland.
- 88Translational Laboratory in Genetic Medicine (TLGM), Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
- 89Jackson Heart Study, University of Mississippi Medical Center, Jackson, Mississippi, USA.
- 90College of Public Services, Jackson State University, Jackson, Mississippi, USA.
- 91KG Jebsen Center for Diabetes Research, Department of Clinical Science, University of Bergen, Bergen, Norway.
- 92Department of Pediatrics, Haukeland University Hospital, Bergen, Norway.
- 93NIHR Biomedical Research Centre at Guy's and St Thomas' Foundation Trust, London, UK.
- 94Institute of Human Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
- 95Department of Clinical Sciences, Diabetes and Endocrinology, Lund University Diabetes Centre, Malmö, Sweden.
- 96Institute of Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany.
- 97German Center for Diabetes Research (DZD), München-Neuherberg, Germany.
- 98Institute of Regional Health Research, University of Southern Denmark, Odense, Denmark.
- 99Department of Clinical Biochemistry, Vejle Hospital, Vejle, Denmark.
- 100Department of Internal Medicine and Endocrinology, Vejle Hospital, Vejle, Denmark.
- 101Department of Health, National Institute for Health and Welfare, Helsinki, Finland.
- 102Abdominal Center: Endocrinology, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
- 103Minerva Foundation Institute for Medical Research, Helsinki, Finland.
- 104Department of Medicine, University of Helsinki and Helsinki University Central Hospital, Helsinki, Finland.
- 105Division of Cardiovascular and Diabetes Medicine, Medical Research Institute, Ninewells Hospital and Medical School, Dundee, UK.
- 106Estonian Genome Center, University of Tartu, Tartu, Estonia.
- 107Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
- 108Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts, USA.
- 109Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.
- 110Folkhälsan Research Centre, Helsinki, Finland.
- 111Research Programs Unit, Diabetes and Obesity, University of Helsinki, Helsinki, Finland.
- 112Steno Diabetes Center, Gentofte, Denmark.
- 113Research Centre for Prevention and Health, Capital Region of Denmark, Glostrup, Denmark.
- 114Department of Public Health, Institute of Health Sciences, University of Copenhagen, Copenhagen, Denmark.
- 115Faculty of Medicine, Aalborg University, Aalborg, Denmark.
- 116Department of Primary Health Care, Vaasa Central Hospital, Vaasa, Finland.
- 117Diabetes Center, Vaasa Health Care Center, Vaasa, Finland.
- 118Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
- 119Research Unit of Molecular Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
- 120Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University, Düsseldorf, Germany.
- 121Department of Public Health, Section of General Practice, Aarhus University, Aarhus, Denmark.
- 122Department of Clinical Experimental Research, Rigshospitalet, Glostrup, Denmark.
- 123Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
- 124Department of Clinical Sciences, Hypertension and Cardiovascular Disease, Lund University, Malmö, Sweden.
- 125Oxford NIHR Biomedical Research Centre, Oxford University Hospitals Trust, Oxford, UK.
- 126Department of Clinical Sciences, Diabetes and Cardiovascular Disease, Genetic Epidemiology, Lund University, Malmö, Sweden.
- 127Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA.
- 128Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
- 129Department of Epidemiology and Population Health, Albert Einstein College of Medicine, New York, USA.
- 130Division of Endocrinology and Diabetology, Medical Faculty, Heinrich-Heine University, Düsseldorf, Germany.
- 131Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden.
- 132High Throughput Genomics, Oxford Genomics Centre, Wellcome Trust Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
- 133Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
- 134Center of Life and Food Sciences Weihenstephan, Technische Universität München, Freising-Weihenstephan, Germany.
- 135William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK.
- 136Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD), King Abdulaziz University, Jeddah, Saudi Arabia.
- 137Department of Clinical Sciences, Medicine, Lund University, Malmö, Sweden.
- 138Faculty of Health Sciences, University of Southern Denmark, Odense, Denmark.
- 139Department of Social Services and Health Care, Jakobstad, Finland.
- 140Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Cambridge, UK.
- 141Pat Macpherson Centre for Pharmacogenetics and Pharmacogenomics, Medical Research Institute, Ninewells Hospital and Medical School, Dundee, UK.
- 142Foundation for Research in Health, Exercise and Nutrition, Kuopio Research Institute of Exercise Medicine, Kuopio, Finland.
- 143Center for Vascular Prevention, Danube University Krems, Krems, Austria.
- 144Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia.
- 145Dasman Diabetes Institute, Dasman, Kuwait.
- 146National Institute for Health and Welfare, Helsinki, Finland.
- 147Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
- 148Department of Physiology & Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
- 149Diabetes and Obesity Research Institute, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
- 150Department of Medical Sciences, Molecular Medicine and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
- 151Cedars-Sinai Diabetes and Obesity Research Institute, Los Angeles, California, USA.
- 152Functional Genomics Unit, CSIR-Institute of Genomics & Integrative Biology (CSIR-IGIB), New Delhi, India.
- 153Department of Biomedical Science, Hallym University, Chuncheon, Republic of Korea.
- 154CSIR-Centre for Cellular and Molecular Biology, Hyderabad, Telangana, India.
- 155Li Ka Shing Institute of Health Sciences, The Chinese University of Hong Kong, Hong Kong, China.
- 156Hong Kong Institute of Diabetes and Obesity, The Chinese University of Hong Kong, Hong Kong, China.
- 157MRC-PHE Centre for Environment and Health, Imperial College London, London, UK.
- 158The Biostatistics Center, The George Washington University, Rockville, Maryland, USA.
- 159Department of Medicine, Division of Endocrinology, Diabetes and Nutrition, and Program in Personalized and Genomic Medicine, University of Maryland School of Medicine, Baltimore, Maryland, USA.
- 160Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India.
- 161Department of Genomics of Common Disease, School of Public Health, Imperial College London, London, UK.
- 162Life Sciences Institute, National University of Singapore, Singapore, Singapore.
- 163Department of Statistics and Applied Probability, National University of Singapore, Singapore, Singapore.
- 164Endocrinology and Metabolism Service, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
- 165The Medical School, Institute of Cellular Medicine, Newcastle University, Newcastle, UK.
- 166Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
- 167Hannover Unified Biobank, Hannover Medical School, Hanover, Germany.
- 168Department of Human Genetics, Hannover Medical School, Hanover, Germany.
- 169Department of Medical Sciences, Uppsala University, Uppsala, Sweden.
- 170Data Sciences and Data Engineering, Broad Institute, Cambridge, Massachusetts, USA.
- 171Finnish Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland.
- 172Imperial College Healthcare NHS Trust, Imperial College London, London, UK.
- 173Clinical Research Centre, Centre for Molecular Medicine, Ninewells Hospital and Medical School, Dundee, UK.
- 174The Usher Institute to the Population Health Sciences and Informatics, University of Edinburgh, Edinburgh, UK.
- 175University of Exeter Medical School, University of Exeter, Exeter, UK.
- 176Department of Natural Science, University of Haifa, Haifa, Israel.
- 177Institute of Human Genetics, Technische Universität München, Munich, Germany.
- 178Departments of Medicine and Human Genetics, The University of Chicago, Chicago, Illinois, USA.
- 179Cardiovascular & Metabolic Disorders Program, Duke-NUS Medical School Singapore, Singapore, Singapore.
- 180Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK.
- 181Department of Physiology and Biophysics, University of Mississippi Medical Center, Jackson, Mississippi, USA.
- 182Department of Laboratory Medicine & Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA.
- 183Blood Systems Research Institute, San Francisco, California, USA.
- 184General Medicine Division, Massachusetts General Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
- 185Division of Endocrinology and Metabolism, Department of Medicine, McGill University, Montreal, Quebec, Canada.
- 186Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
- 187Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, USA.
- 188Department of Biostatistics, University of Liverpool, Liverpool, UK.
- 189Department of Medicine, Harvard Medical School, Boston, Massachusetts, USA.
- 190Diabetes Research Center (Diabetes Unit), Department of Medicine, Massachusetts General Hospital, Boston, Massachusetts, USA.
- 191Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA.
Abstract
To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (>80% of low-frequency coding variants in ~82 K Europeans via the exome chip, and ~90% of low-frequency non-coding variants in ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.
Conflict of interest statement
Ralph A DeFronzo has been a member of advisory boards for Astra Zeneca, Novo Nordisk, Janssen, Lexicon, Boehringer-Ingelheim, received research support from Bristol Myers Squibb, Boehringer- Ingelheim, Takeda and Astra Zeneca, and is a member of speaker’s bureaus for Novo-Nordisk and Astra Zeneca. Jose C Florez has received consulting honoraria from Pfizer and PanGenX. Erik Ingelsson is an advisor and consultant for Precision Wellness, Inc., and advisor for Cellink for work unrelated to the present project. Mark McCarthy has received consulting and advisory board honoraria from Pfizer, Lilly, and NovoNordisk. Gilean McVean and Peter Donnelly are co-founders of Genomics PLC, which provides genome analytics.
Similar articles
The genetic architecture of type 2 diabetes.
Fuchsberger C, Flannick J, Teslovich TM, Mahajan A, Agarwala V, Gaulton KJ, Ma C, Fontanillas P, Moutsianas L, McCarthy DJ, Rivas MA, Perry JRB, Sim X, Blackwell TW, Robertson NR, Rayner NW, Cingolani P, Locke AE, Tajes JF, Highland HM, Dupuis J, Chines PS, Lindgren CM, Hartl C, Jackson AU, Chen H, Huyghe JR, van de Bunt M, Pearson RD, Kumar A, Müller-Nurasyid M, Grarup N, Stringham HM, Gamazon ER, Lee J, Chen Y, Scott RA, Below JE, Chen P, Huang J, Go MJ, Stitzel ML, Pasko D, Parker SCJ, Varga TV, Green T, Beer NL, Day-Williams AG, Ferreira T, Fingerlin T, Horikoshi M, Hu C, Huh I, Ikram MK, Kim BJ, Kim Y, Kim YJ, Kwon MS, Lee J, Lee S, Lin KH, Maxwell TJ, Nagai Y, Wang X, Welch RP, Yoon J, Zhang W, Barzilai N, Voight BF, Han BG, Jenkinson CP, Kuulasmaa T, Kuusisto J, Manning A, Ng MCY, Palmer ND, Balkau B, Stančáková A, Abboud HE, Boeing H, Giedraitis V, Prabhakaran D, Gottesman O, Scott J, Carey J, Kwan P, Grant G, Smith JD, Neale BM, Purcell S, Butterworth AS, Howson JMM, Lee HM, Lu Y, Kwak SH, Zhao W, Danesh J, Lam VKL, Park KS, Saleheen D, So WY, Tam CHT, Afzal U, Aguilar D, Arya R, Aung T, Chan E, Navarro C, Cheng CY, Palli D, Correa A, Curran JE, Rybin D, Farook VS, Fowler…See abstract for full author list ➔Nature. 2016 Aug 4;536(7614):41-47. doi: 10.1038/nature18642. Epub 2016 Jul 11.PMID: 27398621 Free PMC article.
Exome sequencing of 20,791 cases of type 2 diabetes and 24,440 controls.
Flannick J, Mercader JM, Fuchsberger C, Udler MS, Mahajan A, Wessel J, Teslovich TM, Caulkins L, Koesterer R, Barajas-Olmos F, Blackwell TW, Boerwinkle E, Brody JA, Centeno-Cruz F, Chen L, Chen S, Contreras-Cubas C, Córdova E, Correa A, Cortes M, DeFronzo RA, Dolan L, Drews KL, Elliott A, Floyd JS, Gabriel S, Garay-Sevilla ME, García-Ortiz H, Gross M, Han S, Heard-Costa NL, Jackson AU, Jørgensen ME, Kang HM, Kelsey M, Kim BJ, Koistinen HA, Kuusisto J, Leader JB, Linneberg A, Liu CT, Liu J, Lyssenko V, Manning AK, Marcketta A, Malacara-Hernandez JM, Martínez-Hernández A, Matsuo K, Mayer-Davis E, Mendoza-Caamal E, Mohlke KL, Morrison AC, Ndungu A, Ng MCY, O'Dushlaine C, Payne AJ, Pihoker C; Broad Genomics Platform; Post WS, Preuss M, Psaty BM, Vasan RS, Rayner NW, Reiner AP, Revilla-Monsalve C, Robertson NR, Santoro N, Schurmann C, So WY, Soberón X, Stringham HM, Strom TM, Tam CHT, Thameem F, Tomlinson B, Torres JM, Tracy RP, van Dam RM, Vujkovic M, Wang S, Welch RP, Witte DR, Wong TY, Atzmon G, Barzilai N, Blangero J, Bonnycastle LL, Bowden DW, Chambers JC, Chan E, Cheng CY, Cho YS, Collins FS, de Vries PS, Duggirala R, Glaser B, Gonzalez C, Gonzalez ME, Groop L, Kooner JS, Kwak SH…See abstract for full author list ➔Nature. 2019 Jun;570(7759):71-76. doi: 10.1038/s41586-019-1231-2. Epub 2019 May 22.PMID: 31118516 Free PMC article.
Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture.
Zheng HF, Forgetta V, Hsu YH, Estrada K, Rosello-Diez A, Leo PJ, Dahia CL, Park-Min KH, Tobias JH, Kooperberg C, Kleinman A, Styrkarsdottir U, Liu CT, Uggla C, Evans DS, Nielson CM, Walter K, Pettersson-Kymmer U, McCarthy S, Eriksson J, Kwan T, Jhamai M, Trajanoska K, Memari Y, Min J, Huang J, Danecek P, Wilmot B, Li R, Chou WC, Mokry LE, Moayyeri A, Claussnitzer M, Cheng CH, Cheung W, Medina-Gómez C, Ge B, Chen SH, Choi K, Oei L, Fraser J, Kraaij R, Hibbs MA, Gregson CL, Paquette D, Hofman A, Wibom C, Tranah GJ, Marshall M, Gardiner BB, Cremin K, Auer P, Hsu L, Ring S, Tung JY, Thorleifsson G, Enneman AW, van Schoor NM, de Groot LC, van der Velde N, Melin B, Kemp JP, Christiansen C, Sayers A, Zhou Y, Calderari S, van Rooij J, Carlson C, Peters U, Berlivet S, Dostie J, Uitterlinden AG, Williams SR, Farber C, Grinberg D, LaCroix AZ, Haessler J, Chasman DI, Giulianini F, Rose LM, Ridker PM, Eisman JA, Nguyen TV, Center JR, Nogues X, Garcia-Giralt N, Launer LL, Gudnason V, Mellström D, Vandenput L, Amin N, van Duijn CM, Karlsson MK, Ljunggren Ö, Svensson O, Hallmans G, Rousseau F, Giroux S, Bussière J, Arp PP, Koromani F, Prince RL, Lewis JR, Langdahl BL, Hermann AP, Jensen JE, Kapto…See abstract for full author list ➔Nature. 2015 Oct 1;526(7571):112-7. doi: 10.1038/nature14878. Epub 2015 Sep 14.PMID: 26367794 Free PMC article.
The Contribution of Low-Frequency and Rare Coding Variation to Susceptibility to Type 2 Diabetes.
Flannick J.Curr Diab Rep. 2019 Apr 8;19(5):25. doi: 10.1007/s11892-019-1142-5.PMID: 30957210 Free PMC article. Review.
Recent advances in understanding the genetic architecture of type 2 diabetes.
Mohlke KL, Boehnke M.Hum Mol Genet. 2015 Oct 15;24(R1):R85-92. doi: 10.1093/hmg/ddv264. Epub 2015 Jul 9.PMID: 26160912 Free PMC article. Review.
Cited by
Deep learning for detection of iso-dense, obscure masses in mammographically dense breasts.
Rangarajan K, Aggarwal P, Gupta DK, Dhanakshirur R, Baby A, Pal C, Gupta AK, Hari S, Banerjee S, Arora C.Eur Radiol. 2023 May 20. doi: 10.1007/s00330-023-09717-7. Online ahead of print.PMID: 37209125
Genetic Polymorphisms and Diversity in Nonalcoholic Fatty Liver Disease (NAFLD): A Mini Review.
Sulaiman SA, Dorairaj V, Adrus MNH.Biomedicines. 2022 Dec 30;11(1):106. doi: 10.3390/biomedicines11010106.PMID: 36672614 Free PMC article. Review.
Prakash T, Ramachandra NB.Avicenna J Med Biotechnol. 2022 Jul-Sep;14(3):239-246. doi: 10.18502/ajmb.v14i3.9831.PMID: 36061131 Free PMC article.
DiCorpo D, Gaynor SM, Russell EM, Westerman KE, Raffield LM, Majarian TD, Wu P, Sarnowski C, Highland HM, Jackson A, Hasbani NR, de Vries PS, Brody JA, Hidalgo B, Guo X, Perry JA, O'Connell JR, Lent S, Montasser ME, Cade BE, Jain D, Wang H, D'Oliveira Albanus R, Varshney A, Yanek LR, Lange L, Palmer ND, Almeida M, Peralta JM, Aslibekyan S, Baldridge AS, Bertoni AG, Bielak LF, Chen CS, Chen YI, Choi WJ, Goodarzi MO, Floyd JS, Irvin MR, Kalyani RR, Kelly TN, Lee S, Liu CT, Loesch D, Manson JE, Minster RL, Naseri T, Pankow JS, Rasmussen-Torvik LJ, Reiner AP, Reupena MS, Selvin E, Smith JA, Weeks DE, Xu H, Yao J, Zhao W, Parker S, Alonso A, Arnett DK, Blangero J, Boerwinkle E, Correa A, Cupples LA, Curran JE, Duggirala R, He J, Heckbert SR, Kardia SLR, Kim RW, Kooperberg C, Liu S, Mathias RA, McGarvey ST, Mitchell BD, Morrison AC, Peyser PA, Psaty BM, Redline S, Shuldiner AR, Taylor KD, Vasan RS, Viaud-Martinez KA, Florez JC, Wilson JG, Sladek R, Rich SS, Rotter JI, Lin X, Dupuis J, Meigs JB, Wessel J, Manning AK.Commun Biol. 2022 Jul 28;5(1):756. doi: 10.1038/s42003-022-03702-4.PMID: 35902682 Free PMC article.
Mutations and variants of ONECUT1 in diabetes.
Philippi A, Heller S, Costa IG, Senée V, Breunig M, Li Z, Kwon G, Russell R, Illing A, Lin Q, Hohwieler M, Degavre A, Zalloua P, Liebau S, Schuster M, Krumm J, Zhang X, Geusz R, Benthuysen JR, Wang A, Chiou J, Gaulton K, Neubauer H, Simon E, Klein T, Wagner M, Nair G, Besse C, Dandine-Roulland C, Olaso R, Deleuze JF, Kuster B, Hebrok M, Seufferlein T, Sander M, Boehm BO, Oswald F, Nicolino M, Julier C, Kleger A.Nat Med. 2021 Nov;27(11):1928-1940. doi: 10.1038/s41591-021-01502-7. Epub 2021 Oct 18.PMID: 34663987 Free PMC article.
KMEL References
References
-
- 2016. The European Genome-phenome Archive. EGAS00001001459
-
- 2016. The European Genome-phenome Archive. EGAS00001001460
-
- Altshuler D., Boehnke M., McCarthy M., Florez J. 2016. dbGAP. phs001097.v1.p1
-
- Altshuler D., Boehnke M., McCarthy M., Florez J. 2016. dbGAP. phs001099.v1.p1
-
- Altshuler D., Boehnke M., McCarthy M., Florez J. 2016. dbGAP. phs001098.v1.p1
-
- Duggirala R. 2016. dbGAP. phs000849.v1.p1
-
- Altshuler D., Boehnke M., McCarthy M., Florez J. 2016. dbGAP. phs001096.v1.p1
-
- Altshuler D., Boehnke M., McCarthy M., Florez J. 2016. dbGAP. phs001095.v1.p1
-
- Altshuler D., Boehnke M., McCarthy M., Florez J. 2016. dbGAP. phs001093.v1.p1
-
- Altshuler D., Boehnke M., McCarthy M., Florez J. 2016. dbGAP. phs001100.v1.p1
-
- Altshuler D., Boehnke M., McCarthy M., Florez J. 2016. dbGAP. phs001102.v1.p1
-
- Altshuler D., Boehnke M., McCarthy M., Florez J. 2016. dbGAP. phs000840.v1.p1