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
- Willems, Sara M.24
- Navarro, Pau26
- Tanaka, Toshiko27
- Jackson, Anne U.28
- Montasser, May E.29
- O’Connell, Jeff R.29
- Bielak, Lawrence F.28
- Webster, Rebecca J.30
- Saxena, Richa31, 32, 33, 34
- Stafford, Jeanette M.35
- Pourcain, Beate St16, 17
- Timpson, Nicholas J.16, 17
- Salo, Perttu36
- Shin, So-Youn37
- Amin, Najaf38
- Smith, Albert V.28, 39, 40
- Li, Guo41, 41
- Verweij, Niek42
- Goel, Anuj1, 43
- Ford, Ian44
- Johnson, Paul C. D.44, 44
- Johnson, Toby45, 45
- Kapur, Karen46
- Thorleifsson, Gudmar47
- Strawbridge, Rona J.48, 49, 44
- Rasmussen-Torvik, Laura J.50
- Esko, Tõnu4
- Mihailov, Evelin4
- Fall, Tove51
- Fraser, Ross M.52, 53
- Mahajan, Anubha1, 54
- Kanoni, Stavroula45, 55
- Giedraitis, Vilmantas56
- Kleber, Marcus E.57
- Silbernagel, Günther58
- Meyer, Julia59
- Müller-Nurasyid, Martina59, 60, 61, 62
- Ganna, Andrea63, 64, 64
- Sarin, Antti-Pekka65, 36
- Yengo, Loic10, 11, 21
- Shungin, Dmitry66, 67, 66
- Luan, Jian’an9
- Horikoshi, Momoko1, 43, 68
- An, Ping69
- Sanna, Serena70, 71
- Boettcher, Yvonne72, 72
- Rayner, N. William1, 55, 43
- Nolte, Ilja M.73
- Zemunik, Tatijana74
- Iperen, Erik van75
- Kovacs, Peter72
- Hastie, Nicholas D.26
- Wild, Sarah H.52
- McLachlan, Stela52
- Campbell, Susan26
- Polasek, Ozren74
- Carlson, Olga76
- Egan, Josephine76
- Kiess, Wieland72, 72
- Willemsen, Gonneke5
- Kuusisto, Johanna77
- Laakso, Markku77
- Dimitriou, Maria78
- Hicks, Andrew A.79
- Rauramaa, Rainer80, 81
- Bandinelli, Stefania82
- Thorand, Barbara8, 59
- Liu, Yongmei35
- Miljkovic, Iva83
- Lind, Lars84
- Doney, Alex85
- Perola, Markus36, 65, 4
- Hingorani, Aroon86
- Kivimaki, Mika86
- Kumari, Meena86, 87
- Bennett, Amanda J.43
- Groves, Christopher J.43
- Herder, Christian8, 88, 89
- Koistinen, Heikki A.90, 91, 92
- Kinnunen, Leena90
- Faire, Ulf de48
- Bakker, Stephan J. L.73
- Uusitupa, Matti93
- Palmer, Colin N. A.85
- Jukema, J. Wouter94, 95
- Sattar, Naveed96
- Pouta, Anneli36, 97
- Snieder, Harold73
- Boerwinkle, Eric98, 99
- Pankow, James S.100
- Magnusson, Patrik K.48
- Krus, Ulrika101
- Scapoli, Chiara13
- de Geus, Eco J. C. N.5, 6
- Blüher, Matthias72, 102
- Wolffenbuttel, Bruce H. R.73
- Province, Michael A.69
- Abecasis, Goncalo R.28
- Meigs, James B.64, 103, 33
- Hovingh, G. Kees104, 105
- Lindström, Jaana106
- Wilson, James F.26, 52
- Wright, Alan F.26
- Dedoussis, George V.78
- Bornstein, Stefan R.107
- Schwarz, Peter E. H.108, 109, 110
- Tönjes, Anke72, 72
- Winkelmann, Bernhard R.111
- Boehm, Bernhard O.112
- März, Winfried57, 113
- Metspalu, Andres4
- Price, Jackie F.52
- Deloukas, Panos45, 55, 114
- Körner, Antje72, 63
- Lakka, Timo A.80, 115
- Keinanen-Kiukaanniemi, Sirkka M.116, 117
- Saaristo, Timo E.118, 119
- Bergman, Richard N.120
- Tuomilehto, Jaakko36, 65, 121, 114
- Wareham, Nicholas J.9
- Langenberg, Claudia9
- Männistö, Satu90
- Franks, Paul W.67, 122, 66
- Hayward, Caroline26
- Vitart, Veronique26
- Kaprio, Jaakko65, 65
- Visvikis-Siest, Sophie23
- Balkau, Beverley123, 124
- Altshuler, David31, 32, 33
- Rudan, Igor52
- Stumvoll, Michael72, 72
- Campbell, Harry52
- van Duijn, Cornelia M.24, 125
- Gieger, Christian7, 8, 59
- Illig, Thomas7, 126, 126
- Ferrucci, Luigi127
- Pedersen, Nancy L.48
- Pramstaller, Peter P.79, 128, 129
- Boehnke, Michael28
- Frayling, Timothy M.130
- Shuldiner, Alan R.29, 131
- Peyser, Patricia A.28
- Kardia, Sharon L. R.28
- Palmer, Lyle J.132
- Penninx, Brenda W.15
- Meneton, Pierre133
- Harris, Tamara B.134
- Navis, Gerjan73
- Harst, Pim van der42, 135
- Smith, George Davey16
- Forouhi, Nita G.9
- Loos, Ruth J. F.9, 136
- Salomaa, Veikko36
- Soranzo, Nicole37
- Boomsma, Dorret I.5
- Groop, Leif65, 101
- Tuomi, Tiinamaija65, 101, 137, 138
- Hofman, Albert38, 139, 140
- Munroe, Patricia B.45, 45
- Gudnason, Vilmundur39, 141
- Siscovick, David S.41, 41, 41
- Watkins, Hugh1, 43
- Lecoeur, Cecile10, 11
- Vollenweider, Peter142
- Franco-Cereceda, Anders48
- Eriksson, Per20
- Jarvelin, Marjo-Riitta19, 116
- Stefansson, Kari47, 143
- Hamsten, Anders48, 49, 49
- Nicholson, George43
- Karpe, Fredrik43, 144
- Dermitzakis, Emmanouil T.145
- Lindgren, Cecilia M.1, 31, 43, 43
- McCarthy, Mark I.1, 43, 144, 54
- Froguel, Philippe10, 11, 19
- Kaakinen, Marika A.19, 146
- Lyssenko, Valeriya101, 147
- Watanabe, Richard M.102, 102, 148
- Ingelsson, Erik51, 149, 150
- Florez, Jose C.32, 63
- Dupuis, Josée151
- Barroso, Inês37, 152, 153
- Morris, Andrew P.1, 4, 154, 155
- Prokopenko, Inga1, 19, 43, 146, 156 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.