Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability
In: Nature Communications, Jg. 12 (2021), Heft 1, S. 1-18
Online
unknown
Zugriff:
Differences between sexes contribute to variation in the levels of fasting glucose and insulin. Epidemiological studies established a higher prevalence of impaired fasting glucose in men and impaired glucose tolerance in women, however, the genetic component underlying this phenomenon is not established. We assess sex-dimorphic (73,089/50,404 women and 67,506/47,806 men) and sex-combined (151,188/105,056 individuals) fasting glucose/fasting insulin genetic effects via genome-wide association study meta-analyses in individuals of European descent without diabetes. Here we report sex dimorphism in allelic effects on fasting insulin at IRS1 and ZNF12 loci, the latter showing higher RNA expression in whole blood in women compared to men. We also observe sex-homogeneous effects on fasting glucose at seven novel loci. Fasting insulin in women shows stronger genetic correlations than in men with waist-to-hip ratio and anorexia nervosa. Furthermore, waist-to-hip ratio is causally related to insulin resistance in women, but not in men. These results position dissection of metabolic and glycemic health sex dimorphism as a steppingstone for understanding differences in genetic effects between women and men in related phenotypes.
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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Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability
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| Autor/in / Beteiligte Person: | Fall, Tove ; Mahajan, Anubha ; Shungin, Dmitry ; Balkau, B. ; Navis, Gerjan ; Metspalu, A. ; Pouta, Anneli ; Hicks, Andrew A. ; Nolte, Ilja M. ; Ford, Ian ; Hingorani, Aroon D. ; Stefan R Bornstein ; Goel, Anuj ; Strawbridge, Rona J. ; Verweij, Niek ; Wild, Sarah H. ; Munroe, Patricia B. ; Harris, T.B. ; Lindström, Jaana ; Pcd., Johnson ; Forouhi, Nita G. ; Meneton, Pierre ; Peyser, Patricia A. ; Sarin, A P. ; Ganna, Andrea ; Frayling, Timothy M. ; Magnusson, Patrik K. E. ; Meyer, Joanne M. ; Liu, Yongmei ; Stafford, Jeanette M. ; Herder, Christian ; Zudina, L ; Stathopoulou, Maria G. ; Montasser, May E. ; Hastie, Nicholas D. ; Barroso, Inês ; Peh., Schwarz ; Meigs, James B. ; Salo, Perttu ; George Davey Smith ; Willemsen, Gonneke ; Groves, Christopher J. ; Erik P A Van Iperen ; Province, M. A. ; Salomaa, Veikko ; Sattar, Naveed ; Sanna, Serena ; Dimitriou, Maria ; Jukema, Joop ; Krus, Ulrika ; Smith, Albert V. ; Laakso, Markku ; Wilson, James F. ; Nicholson, George ; Yengo, Loic ; Zemunik, Tatijana ; Eriksson, Per ; Snieder, Harold ; Pramstaller, Peter P. ; Langenberg, Claudia ; Rauramaa, R. ; Shuldiner, Alan R. ; Navarro, Pau ; Vitart, Veronique ; Fraser, Ross M. ; Isaacs, Aaron ; Lecoeur, C. ; Gådin, Jesper R. ; Price, Jackie F. ; Marullo, Letizia ; Bielak, L.F. ; Keinänen-Kiukaanniemi, Sirkka ; Bonnefond, Amélie ; Stumvoll, Michael ; Faggian, Alessia ; Tönjes, Anke ; Tanaka, Tomohiro ; Kiess, Wieland ; Campbell, Harry ; Dupuis, Josée ; Altshuler, David ; Fadista, João ; März, Winfried ; G K Hovingh ; Illig, Thomas ; Johnson, Toby ; Grallert, H ; Stefansson, Kari ; Mägi, Reedik ; Cna., Palmer ; de Geus Ejcn. ; Müller-Nurasyid, Martina ; Kapur, Karen ; Froguel, Philippe ; Boomsma, Dorret I. ; Franco-Cereceda, Anders ; Kleber, Marcus E. ; Boehnke, M ; Carlson, Olga D. ; Polasek, Ozren ; Morris, Andrew P. ; Doney, Alex S. F. ; Amin, Najaf ; Willems, Sara M. ; Gudnason, Vilmundur ; Florez, Jose C. ; O'Connell, Jeffery R. ; Pedersen, Nancy L. ; Saaristo, T. ; Bhr., Wolffenbuttel ; Uusitupa, M. I. J. ; Jiang, Longda ; Miljkovic, Iva ; Pankow, James S. ; Hayward, Caroline ; Watkins, Hugh ; Lagou, Vasiliki ; Kuusisto, Johanna ; Tuomilehto, Jaakko ; Wright, Alan F. ; Egan, Josephine M. ; Jrb., Perry ; C M van Duijn ; Lyssenko, Valeriya ; Groop, Leif ; Bandinelli, Stefania ; Rayner, Nigel W. ; Esko, Tõnu ; McLachlan, Stela ; Horikoshi, Momoko ; Boerwinkle, Eric ; Jansen, Rick ; Bergman, Richard N. ; Thorleifsson, Gudmar ; Palmer, Lyle J. ; Giedraitis, Vilmantas ; Kovacs, Peter ; Wareham, Nicholas J. ; Ferrucci, Luigi ; N J Timpson ; Rybin, D ; Jackson, Anne U. ; Tuomi, Tiinamaija ; Abecasis, Gonçalo R. ; Pvd., Harst ; Kumari, Meena ; Hofman, Albert ; Scapoli, Chiara ; Mihailov, Evelin ; Min, Josine L. ; Hamsten, Anders ; Hottenga, J J. ; Rjf., Loos ; Lind, Lars ; Ulf de Faire ; Kaprio, Jaakko ; Li, Guo ; Beate St Pourcain ; Gieger, C ; Bennett, Amanda J. ; Ulrich, Anna ; Bouatia-Naji, Nabila ; Männistö, Satu ; Dimas, Antigone S. ; Jarvelin, M R. ; Silbernagel, Günther ; Karpe, F ; Körner, A. ; Siscovick, David S. ; Blüher, M ; Webster, Rebecca J. ; Ingelsson, Erik ; Campbell, Susan ; Kivimäki, Mika ; Rasmussen-Torvik, Laura J. ; Koistinen, Heikki A. ; Visvikis-Siest, Sophie ; Boehm, Bernhard O. ; Prokopenko, Inga ; An, Ping ; Dermitzakis, Emmanouil T. ; Lindgren, Cecilia M. ; Slr., Kardia ; Saxena, Richa ; Rudan, Igor ; Watanabe, Richard M. ; Luan, Jian'an ; Kaakinen, Marika ; Shin, S Y. ; Dedoussis, George ; Deloukas, Panagiotis ; McCarthy, Mark I. ; Thorand, Barbara ; Penninx, B.W.J.H. ; Vollenweider, Peter ; Franks, Paul W. ; Kinnunen, Leena ; Perola, Markus ; Boettcher, Yvonne ; Lakka, Timo A. ; Soranzo, Nicole ; Kanoni, Stavroula ; Sjl., Bakker ; Br, Winkelmann ; The Wellcome Trust Centre for Human Genetics [Oxford] ; University of Oxford [Oxford] ; Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven) ; Institute of Genomics [Tartu, Estonia] ; University of Tartu ; Vrije Universiteit Amsterdam [Amsterdam] (VU) ; Vrije Universiteit Medical Centre (VUMC) ; 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Chan School of Public Health ; John Radcliffe Hospital [Oxford University Hospital] ; Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV) ; Université de Genève (UNIGE) ; Big Data Institute ; University of Surrey (UNIS) ; University of Bergen (UiB) ; Stanford School of Medicine [Stanford] ; Medicine, Stanford ; Stanford University-Stanford University ; Stanford Cardiovascular Institute ; University of Liverpool ; University of Manchester [Manchester] ; Institute of Biochemistry and Genetics of Ufa Scientific Centre ; Russian Academy of Sciences [Moscow] (RAS) ; Experimental Vascular Medicine ; Medicine, Vascular ; ACS - Atherosclerosis & ischemic syndromes ; SIEST, Sofia ; PreciDIAB Institute, the holistic approach of personal diabets care - - PreciDIAB2018 - ANR-18-IBHU-0001 - IBHU - VALID ; Understanding the dynamic determinants of glucose homeostasis and social capability to promote Healthy and active aging - DYNAHEALTH - - H20202015-04-01 - 2019-03-31 - 633595 -, VALID ; Beyond the Genetics of Addiction - ADDICTION - - EC:FP7:ERC2011-12-01 - 2017-05-31 - 284167 -, VALID ; Rise of scientific excellence and collaboration for implementing personalised medicine in Estonia - ePerMed - - H20202016-01-01 - 2018-12-31 - 692145 -, VALID ; University of Oxford ; Helmholtz Zentrum München = German Research Center for Environmental Health ; Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)) ; Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité) ; Università degli Studi di Ferrara = University of Ferrara (UniFE) ; Université de Lausanne = University of Lausanne (UNIL) ; Graz, Karl-Franzens-Universität ; Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU) ; Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki ; Helsingin yliopisto = Helsingfors universitet = University of Helsinki ; Amsterdam UMC - Amsterdam University Medical Center ; Nanyang Technological University [Singapour] ; Universität zu Lübeck = University of Lübeck [Lübeck] ; Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS) ; Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Sorbonne Paris Nord ; Université de Genève = University of Geneva (UNIGE) ; ANR-18-IBHU-0001,PreciDIAB,PreciDIAB Institute, the holistic approach of personal diabets care(2018) ; European Project: 633595,H2020,H2020-PHC-2014-two-stage,DYNAHEALTH(2015) ; European Project: 284167,EC:FP7:ERC,ERC-2011-StG_20101124,ADDICTION(2011) ; European Project: 692145,H2020,H2020-TWINN-2015,ePerMed(2016) ; Psychology, Biological ; APH - Health Behaviors & Chronic Diseases ; APH - Personalized Medicine ; Genomics, Functional ; APH - Mental Health ; Sociology and Social Gerontology ; APH - Methodology ; Hottenga, Jouke- Jan [0000-0002-5668-2368] ; Bouatia-Naji, Nabila [0000-0001-5424-2134] ; Jansen, Rick [0000-0002-3333-6737] ; Min, Josine L. 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[0000-0003-1015-0531] ; Ingelsson, Erik [0000-0003-2256-6972] ; Dupuis, Josée [0000-0003-2871-3603] ; Barroso, Inês [0000-0001-5800-4520] ; Apollo - University of Cambridge Repository ; Epidemiology ; University Hospital Mannheim | Universitätsmedizin Mannheim ; National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR) ; Leipzig, Universität ; Leiden, Universiteit ; Universität Heidelberg [Heidelberg] = Heidelberg University ; Karl-Franzens-Universität [Grazriche] ; Psychiatry ; Amsterdam Neuroscience - Complex Trait Genetics ; Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep ; practice, General ; APH - Digital Health ; Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI) ; Life Course Epidemiology (LCE) ; Lifestyle Medicine (LM) ; Groningen Institute for Organ Transplantation (GIOT) ; Groningen Kidney Center (GKC) ; Center for Liver, Digestive and Metabolic Diseases (CLDM) ; Value, Affordability and Sustainability (VALUE) ; Cardiovascular Centre (CVC) ; Hottenga, Jouke-Jan [0000-0002-5668-2368] ; Min, Josine L [0000-0003-4456-9824] ; Willems, Sara M [0000-0002-6803-3007] ; Jackson, Anne U [0000-0002-9672-2547] ; Bielak, Lawrence F [0000-0002-3443-8030] ; Smith, Albert V [0000-0003-1942-5845] ; Johnson, Paul CD [0000-0001-6663-7520] ; Strawbridge, Rona J [0000-0001-8506-3585] ; Fraser, Ross M [0000-0003-0488-2592] ; Kleber, Marcus E [0000-0003-0663-7275] ; Luan, Jian'an [0000-0003-3137-6337] ; Nolte, Ilja M [0000-0001-5047-4077] ; Wild, Sarah H [0000-0001-7824-2569] ; Hicks, Andrew A [0000-0001-6320-0411] ; Koistinen, Heikki A [0000-0001-7870-070X] ; Bakker, Stephan JL [0000-0003-3356-6791] ; Palmer, Colin NA [0000-0002-6415-6560] ; Jukema, J Wouter [0000-0002-3246-8359] ; Magnusson, Patrik K [0000-0002-7315-7899] ; Wolffenbuttel, Bruce HR [0000-0001-9262-6921] ; Abecasis, Goncalo R [0000-0003-1509-1825] ; Meigs, James B [0000-0002-2439-2657] ; Wilson, James F [0000-0001-5751-9178] ; Schwarz, Peter EH [0000-0001-6317-7880] ; Boehm, Bernhard O [0000-0002-2706-7710] ; Wareham, Nicholas J [0000-0003-1422-2993] ; Franks, Paul W [0000-0002-0520-7604] ; van Duijn, Cornelia M [0000-0002-2374-9204] ; Pramstaller, Peter P [0000-0002-9831-8302] ; Frayling, Timothy M [0000-0001-8362-2603] ; Peyser, Patricia A [0000-0002-9717-8459] ; Forouhi, Nita G [0000-0002-5041-248X] ; Loos, Ruth JF [0000-0002-8532-5087] ; Boomsma, Dorret I [0000-0002-7099-7972] ; Munroe, Patricia B [0000-0002-4176-2947] ; Dermitzakis, Emmanouil T [0000-0002-9302-6490] ; Lindgren, Cecilia M [0000-0002-4903-9374] ; Kaakinen, Marika A [0000-0002-9228-0462] ; Watanabe, Richard M [0000-0003-1015-0531] ; University, Tampere ; Tays Research Services ; Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC) ; Fysiologie ; RS: FHML MaCSBio ; RS: Carim - B01 Blood proteins & engineering |
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| Zeitschrift: | Nature Communications, Jg. 12 (2021), Heft 1, S. 1-18 |
| Veröffentlichung: | HAL CCSD, 2021 |
| Medientyp: | unknown |
| ISSN: | 2041-1723 (print) |
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