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Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability

Authors
  • Lagou, Vasiliki1, 2, 3
  • Mägi, Reedik4
  • Hottenga, Jouke- Jan5, 6
  • Grallert, Harald7, 8
  • Perry, John R. B.9
  • Bouatia-Naji, Nabila10, 11, 12
  • Marullo, Letizia13
  • Rybin, Denis14
  • Jansen, Rick15
  • Min, Josine L.16, 17
  • Dimas, Antigone S.18
  • Ulrich, Anna19
  • Zudina, Liudmila19
  • Gådin, Jesper R.20
  • Jiang, Longda19, 21
  • Faggian, Alessia19
  • Bonnefond, Amélie10, 11, 19
  • Fadista, Joao22
  • Stathopoulou, Maria G.23
  • Isaacs, Aaron24, 25, 25
  • And 184 more
  • 1 University of Oxford, Oxford, United Kingdom , Oxford (United Kingdom)
  • 2 Laboratory of Adaptive Immunity, Leuven, KU Leuven, Belgium , Leuven (Belgium)
  • 3 VIB-KU Leuven Center for Brain and Disease Research, Leuven, Belgium , Leuven (Belgium)
  • 4 University of Tartu, Tartu, Estonia , Tartu (Estonia)
  • 5 Vrije Universiteit, Amsterdam, the Netherlands , Amsterdam (Netherlands)
  • 6 VU University medical center, Amsterdam, the Netherlands , Amsterdam (Netherlands)
  • 7 Helmholtz Zentrum München Research Center for Environmental Health, Neuherberg, Germany , Neuherberg (Germany)
  • 8 German Center for Diabetes Research (DZD, München-Neuherberg, Germany , München-Neuherberg (Germany)
  • 9 University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom , Cambridge (United Kingdom)
  • 10 University of Lille Nord de France, Lille, France , Lille (France)
  • 11 CNRS UMR8199, Institut Pasteur de Lille, Lille, France , Lille (France)
  • 12 INSERM U970, Paris Cardiovascular Research Center PARCC, Paris, 75006, France , Paris (France)
  • 13 University of Ferrara, Ferrara, Italy , Ferrara (Italy)
  • 14 Boston University Data Coordinating Center, Boston, MA, USA , Boston (United States)
  • 15 VU University Medical Center, Amsterdam, the Netherlands , Amsterdam (Netherlands)
  • 16 University of Bristol, Bristol, UK , Bristol (United Kingdom)
  • 17 University of Bristol, Bristol, United Kingdom , Bristol (United Kingdom)
  • 18 Biomedical Sciences Research Center Al. Fleming, Vari, Greece , Vari (Greece)
  • 19 Imperial College London, London, UK , London (United Kingdom)
  • 20 Karolinska University Hospital, Solna, Sweden , Solna (Sweden)
  • 21 The University of Queensland, Brisbane, QLD, 4072, Australia , Brisbane (Australia)
  • 22 Statens Serum Institut, Copenhagen, Denmark , Copenhagen (Denmark)
  • 23 Université de Lorraine, IGE-PCV, Nancy, F-54000, France , Nancy (France)
  • 24 Erasmus Medical Center, Rotterdam, the Netherlands , Rotterdam (Netherlands)
  • 25 Maastricht University, Maastricht, the Netherlands , Maastricht (Netherlands)
  • 26 University of Edinburgh, Western General Hospital, Edinburgh, UK , Edinburgh (United Kingdom)
  • 27 National Institute on Aging, Baltimore, MD, USA , Baltimore (United States)
  • 28 University of Michigan, Ann Arbor, MI, USA , Ann Arbor (United States)
  • 29 University of Maryland, School of Medicine, Baltimore, MD, USA , Baltimore (United States)
  • 30 University of Western Australia Centre for Medical Research, Nedlands, WA, Australia , Nedlands (Australia)
  • 31 Broad Institute of Harvard and Massachusetts Institute of Technology (MIT), Cambridge, MA, USA , Cambridge (United States)
  • 32 Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA, USA , Boston (United States)
  • 33 Harvard Medical School, Boston, MA, USA , Boston (United States)
  • 34 Critical Care and Pain Medicine, MGH, Boston, MA, USA , Boston (United States)
  • 35 Wake Forest University School of Medicine, Winston-Salem, NC, USA , Winston-Salem (United States)
  • 36 Finnish Institute for Health and Welfare, Helsinki, Finland , Helsinki (Finland)
  • 37 Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK , Hinxton (United Kingdom)
  • 38 Department of Epidemiology Erasmus MC, Rotterdam, the Netherlands , Rotterdam (Netherlands)
  • 39 Icelandic Heart Association, Kopavogur, Iceland , Kopavogur (Iceland)
  • 40 University of Iceland, Reykjavik, Iceland , Reykjavik (Iceland)
  • 41 University of Washington, Seattle, WA, USA , Seattle (United States)
  • 42 University of Groningen, University Medical Center Groningen, Groningen, The Netherlands , Groningen (Netherlands)
  • 43 University of Oxford, Oxford, UK , Oxford (United Kingdom)
  • 44 University of Glasgow, Glasgow, UK , Glasgow (United Kingdom)
  • 45 Queen Mary University of London, London, UK , London (United Kingdom)
  • 46 University of Lausanne, Lausanne, Switzerland , Lausanne (Switzerland)
  • 47 deCODE Genetics, Reykjavik, Iceland , Reykjavik (Iceland)
  • 48 Karolinska Institutet, Stockholm, Sweden , Stockholm (Sweden)
  • 49 Karolinska University Hospital Solna, Stockholm, Sweden , Stockholm (Sweden)
  • 50 Northwestern University Feinberg School of Medicine, Chicago, IL, USA , Chicago (United States)
  • 51 Uppsala University, Uppsala, Sweden , Uppsala (Sweden)
  • 52 University of Edinburgh, Edinburgh, UK , Edinburgh (United Kingdom)
  • 53 Synpromics Ltd, Roslin Innovation Centre, Easter Bush Campus, Edinburgh, EH25 9RG, UK , Edinburgh (United Kingdom)
  • 54 Genentech, 340 Point San Bruno Boulevard, South San Francisco, CA, 94080, USA , South San Francisco (United States)
  • 55 Wellcome Trust Sanger Institute, Hinxton, UK , Hinxton (United Kingdom)
  • 56 Uppsala Universitet, Uppsala, Sweden , Uppsala (Sweden)
  • 57 Heidelberg University, Mannheim, Germany , Mannheim (Germany)
  • 58 Medical University of Graz, Graz, Austria , Graz (Austria)
  • 59 German Research Center for Environmental Health, Neuherberg, Germany , Neuherberg (Germany)
  • 60 Ludwig-Maximilians-Universität, Munich, Germany , Munich (Germany)
  • 61 University Hospital Grosshadern, Ludwig-Maximilians-University, Munich, Germany , Munich (Germany)
  • 62 Johannes Gutenberg University, Mainz, 55101, Germany , Mainz (Germany)
  • 63 Massachusetts General Hospital, Boston, MA, USA , Boston (United States)
  • 64 Broad Institute of MIT and Harvard, Cambridge, MA, USA , Cambridge (United States)
  • 65 University of Helsinki, Helsinki, Finland , Helsinki (Finland)
  • 66 Umeå University, Umeå, Sweden , Umeå (Sweden)
  • 67 Skåne University Hospital Malmö, Malmö, Sweden , Malmö (Sweden)
  • 68 RIKEN, Center for Integrative Medical Sciences, Laboratory for Endocrinology, Metabolism and Kidney Disease, Yokohama, Japan , Yokohama (Japan)
  • 69 Washington University School of Medicine, St. Louis, MO, USA , St. Louis (United States)
  • 70 Istituto di Ricerca Genetica e Biomedica, CNR, Monserrato, Italy , Monserrato (Italy)
  • 71 University of Groningen, Groningen, the Netherlands , Groningen (Netherlands)
  • 72 University of Leipzig, Leipzig, Germany , Leipzig (Germany)
  • 73 University of Groningen, University Medical Center Groningen, Groningen, the Netherlands , Groningen (Netherlands)
  • 74 University of Split, Split, Croatia , Split (Croatia)
  • 75 University of Amsterdam, Amsterdam, the Netherlands , Amsterdam (Netherlands)
  • 76 National Institute of Aging, Baltimore, MD, USA , Baltimore (United States)
  • 77 University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland , Kuopio (Finland)
  • 78 Harokopio University, Athens, Greece , Athens (Greece)
  • 79 European Academy Bozen/Bolzano (EURAC) (Affiliated Institute of the University of LübeckLübeckGermany), Bolzano, Italy , Bolzano (Italy)
  • 80 Kuopio Research Institute of Exercise Medicine, Kuopio, Finland , Kuopio (Finland)
  • 81 Kuopio University Hospital, Kuopio, Finland , Kuopio (Finland)
  • 82 Geriatric Unit, Azienda Sanitaria Firenze (ASF), Florence, Italy , Florence (Italy)
  • 83 University of Pittsburgh, Pittsburgh, PA, USA , Pittsburgh (United States)
  • 84 Uppsala University, Akademiska sjukhuset, Uppsala, Sweden , Uppsala (Sweden)
  • 85 University of Dundee, Dundee, UK , Dundee (United Kingdom)
  • 86 University College London, London, UK , London (United Kingdom)
  • 87 University of Essex, Wivenhoe Park, Colchester, Essex, UK , Colchester (United Kingdom)
  • 88 Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Düsseldorf, Germany , Düsseldorf (Germany)
  • 89 Heinrich Heine University Düsseldorf, Düsseldorf, Germany , Düsseldorf (Germany)
  • 90 Finnish Institute for Health and Welfare, Helsinki, FI-00271, Finland , Helsinki (Finland)
  • 91 University of Helsinki and Helsinki University Central Hospital, Haartmaninkatu 4, Helsinki, FI-00029, Finland , Helsinki (Finland)
  • 92 Minerva Foundation Institute for Medical Research, Biomedicum 2U, Tukholmankatu 8, Helsinki, FI-00290, Finland , Helsinki (Finland)
  • 93 University of Eastern Finland, Kuopio, Finland , Kuopio (Finland)
  • 94 Leiden University Medical Center, Leiden, the Netherlands , Leiden (Netherlands)
  • 95 Netherlands Heart Institute, Utrecht, the Netherlands , Utrecht (Netherlands)
  • 96 University of Glasgow, Glasgow, United Kingdom , Glasgow (United Kingdom)
  • 97 Oulu University Hospital and University of Oulu, Oulu, Finland , Oulu (Finland)
  • 98 IMM Center for Human Genetics, University of Texas Health Science Center at Houston, Houston, TX, USA , Houston (United States)
  • 99 University of Texas Health Science Center at Houston, Houston, TX, USA , Houston (United States)
  • 100 University of Minnesota, Minneapolis, MiI, USA , Minneapolis (United States)
  • 101 University Hospital Malmö, Lund University, Malmö, Sweden , Malmö (Sweden)
  • 102 Keck School of Medicine of USC, Los Angeles, CA, USA , Los Angeles (United States)
  • 103 General Medicine Division, Massachusetts General Hospital, Boston, MA, USA , Boston (United States)
  • 104 Amsterdam UMC, Amsterdam, the Netherlands , Amsterdam (Netherlands)
  • 105 Novo Nordisk A/S, Copenhagen, Denmark , Copenhagen (Denmark)
  • 106 Diabetes Prevention Unit, Helsinki, Finland , Helsinki (Finland)
  • 107 Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany , Dresden (Germany)
  • 108 Technische Universität Dresden, Dresden, Germany , Dresden (Germany)
  • 109 Paul Langerhans Institute Dresden of the Helmholtz Center Munich at University Hospital and Faculty of Medicine, TU Dresden, Dresden, Germany , Dresden (Germany)
  • 110 German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany , Neuherberg (Germany)
  • 111 Cardiology Group, Frankfurt-Sachsenhausen, Germany , Frankfurt-Sachsenhausen (Germany)
  • 112 Nanyang Technological University Singapore and Imperial College London, Singapore, Singapore , Singapore (Singapore)
  • 113 Synlab Academy, Synlab Holding Deutschland GmbH, Mannheim, Germany , Mannheim (Germany)
  • 114 King Abdulaziz University, Jeddah, Saudi Arabia , Jeddah (Saudi Arabia)
  • 115 University of Eastern Finland, Kuopio Campus, Kuopio, Finland , Kuopio (Finland)
  • 116 University of Oulu, Oulu, Finland , Oulu (Finland)
  • 117 Oulu University Hospital, Oulu, Finland , Oulu (Finland)
  • 118 Finnish Diabetes Association, Tampere, Finland , Tampere (Finland)
  • 119 Pirkanmaa Hospital District, Tampere, Finland , Tampere (Finland)
  • 120 Cedars-Sinai Medical Center, Los Angeles, CA, USA , Los Angeles (United States)
  • 121 Danube-University Krems, Krems, Austria , Krems (Austria)
  • 122 Harvard School of Public Health, Boston, MA, USA , Boston (United States)
  • 123 Inserm, CESP Center for Research in Epidemiology and Public Health, Villejuif, U1018, France , Villejuif (France)
  • 124 Univ Paris-Saclay, Univ Paris Sud, UVSQ, UMRS 1018, UMRS 1018, Villejuif, France , Villejuif (France)
  • 125 Centre for Medical Systems Biology, Leiden, the Netherlands , Leiden (Netherlands)
  • 126 Hannover Medical School, Hannover, Germany , Hannover (Germany)
  • 127 National Institute on Aging, Baltimore, Maryland, USA , Baltimore (United States)
  • 128 General Central Hospital, Bolzano, Italy , Bolzano (Italy)
  • 129 University of Lübeck, Lübeck, Germany , Lübeck (Germany)
  • 130 University of Exeter, Exeter, UK , Exeter (United Kingdom)
  • 131 Regeneron Pharmaceuticals, Tarrytown, NY, USA , Tarrytown (United States)
  • 132 University of Adelaide, Adelaide, Australia , Adelaide (Australia)
  • 133 Centre de Recherche des Cordeliers, Paris, 75006, France , Paris (France)
  • 134 National Institute on Aging, Bethesda, MD, USA , Bethesda (United States)
  • 135 University Medical Center Groningen, University of Groningen, Groningen, the Netherlands , Groningen (Netherlands)
  • 136 Icahn School of Medicine at Mount Sinai, New York, NY, USA , New York (United States)
  • 137 University of Helsinki and Helsinki University Hospital, Helsinki, Finland , Helsinki (Finland)
  • 138 University of Helsinki and Folkhälsan Research Center, Helsinki, Finland , Helsinki (Finland)
  • 139 Netherlands Consortium for healthy ageing, the Hague, the Netherlands , the Hague (Netherlands)
  • 140 Harvard T.H. Chan School of Public Health, Boston, USA , Boston (United States)
  • 141 Faculty of Medicine University of Iceland, Reykjavik, Iceland , Reykjavik (Iceland)
  • 142 University Hospital Lausanne, Lausanne, Switzerland , Lausanne (Switzerland)
  • 143 University of Iceland, Reykjavík, Iceland , Reykjavík (Iceland)
  • 144 Churchill Hospital, Oxford, UK , Oxford (United Kingdom)
  • 145 University of Geneva Medical School, Geneva, Switzerland , Geneva (Switzerland)
  • 146 University of Surrey, Guildford, UK , Guildford (United Kingdom)
  • 147 University of Bergen, Bergen, Norway , Bergen (Norway)
  • 148 USC Diabetes and Obesity Research Institute, Los Angeles, CA, USA , Los Angeles (United States)
  • 149 Stanford University School of Medicine, Stanford, CA, USA , Stanford (United States)
  • 150 Stanford University, Stanford, CA, 94305, USA , Stanford (United States)
  • 151 Boston University School of Public Health, Boston, MA, USA , Boston (United States)
  • 152 Wellcome Trust-MRC Institute of Metabolic Science, Cambridge, UK , Cambridge (United Kingdom)
  • 153 University of Exeter Medical School, Exeter, UK , Exeter (United Kingdom)
  • 154 University of Liverpool, Liverpool, UK , Liverpool (United Kingdom)
  • 155 The University of Manchester, Manchester, UK , Manchester (United Kingdom)
  • 156 Ufa Federal Research Centre Russian Academy of Sciences, Ufa, Russian Federation , Ufa (Russia)
Type
Published Article
Journal
Nature Communications
Publisher
Springer Nature
Publication Date
Jan 05, 2021
Volume
12
Issue
1
Identifiers
DOI: 10.1038/s41467-020-19366-9
Source
Springer Nature
License
Green

Abstract

Sex differences in fasting glucose and insulin have been identified, but the genetic loci underlying these differences have not. Here, the authors perform a meta-analysis of genome-wide association studies to detect sex-specific and sex-dimorphic loci associated with fasting glucose and insulin.

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