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

V Lagou; Reedik Magi; JJ Hottenga; Harald Grallert; John R. Perry; Nabila Bouatia-Naji; Letizia Marullo; Denis Rybin; R Jansen; JL Min; AS Dimas; ANNA ULRICH; LIUDMILA  ZUDINA; Jesper R Gådin; Longda Jiang; Alessia Faggian; Amélie Bonnefond; Joao Fadista; Maria G Stathopoulou; Aaron Isaacs; SM Willems; Pau Navarro; T Tanaka; Anne U Jackson; May E Montasser; Jeff R O'Connell; Lawrence F Bielak; R. Webster; Richa Saxena; Jeanette M Stafford; Beate St Pourcain; Nicholas J. Timpson; Perttu Salo; SY Shin; Najaf Amin; Albert V Smith; Guo Li; Niek Verweij; Anuj Goel; Ian Ford; Paul C D Johnson; T Johnson; Karen Kapur; G Thorleifsson; RJ Strawbridge; Laura J Rasmussen-Torvik; Tõnu Esko; Evelin Mihailov; T Fall; Ross M Fraser; A Mahajan; Stavroula Kanoni; Vilmantas Giedraitis; ME Kleber; Günther Silbernagel; Julia Meyer; Martina Müller-Nurasyid; Andrea Ganna; Antti-Pekka Sarin; Loic Yengo; Dmitry Shungin; J Luan; Momoko Horikoshi; Ping An; S Sanna; Yvonne Boettcher; NW Rayner; Ilja M Nolte; Tatijana Zemunik; Erik van Iperen; Peter Kovacs; Nicholas D Hastie; SH Wild; Stela McLachlan; SS Campbell; Ozren Polasek; Olga Carlson; Josephine Egan; Wieland Kiess; G Willemsen; Johanna Kuusisto; Markku Laakso; Maria Dimitriou; A Hicks; Rainer Rauramaa; S Bandinelli; B Thorand; Yongmei Liu; Iva Miljkovic; L Lind; Alex Doney; M Perola; AD Hingorani; M Kivimäki; Meena Kumari; Amanda J Bennett; C Groves; C Herder; Heikki A Koistinen; Leena Kinnunen; Ulf de Faire; Stephan J L Bakker; Matti Uusitupa; Colin N. A Palmer; J Wouter Jukema; N Sattar; A Pouta; H Snieder; E Boerwinkle; James S Pankow; PK Magnusson; Ulrika Krus; Chiara Scapoli; Eco J C N de Geus; Matthias Blüher; Bruce H R Wolffenbuttel; Michael A Province; G Abecasis; James B Meigs; G Kees Hovingh; Jaana Lindström; James F Wilson; Alan F Wright; GV Dedoussis; Stefan R Bornstein; Peter E H Schwarz; Anke Tönjes; BR Winkelmann; B Boehm; W März; Andres Metspalu; Jackie F Price; P Deloukas; Antje Körner; Timo A. Lakka; Sirkka M Keinanen-Kiukaanniemi; Timo E Saaristo; Richard N Bergman; J Tuomilehto; N Wareham; Claudia Langenberg; S Männistö; Paul Franks; C Hayward; Veronique Vitart; J Kaprio; Sophie Visvikis-Siest; Beverley Balkau; D Altshuler; Igor Rudan; Michael Stumvoll; Harry Campbell; Cornelia van Duijn; C Gieger; T Illig; L Ferrucci; NL Pedersen; Peter P Pramstaller; Michael Boehnke; Timothy M. Frayling; AR Shuldiner; Patricia A Peyser; Sharon L R Kardia; Lyle J. Palmer; BW Penninx; Pierre Meneton; T Harris; G Navis; Pim van der Harst; George Davey Smith; NG Forouhi; Ruth J F Loos; V Salomaa; N Soranzo; D Boomsma; Leif Groop; Tiinamaija Tuomi; Albert Hofman; Patricia B. Munroe; V Gudnason; DS Siscovick; H Watkins; Cecile Lecoeur; P Vollenweider; A Franco-Cereceda; P Eriksson; Marjo-Riitta Jarvelin; K Stefansson; A Hamsten; G Nicholson; Fredrik Karpe; ET Dermitzakis; C Lindgren; MI McCarthy; P Froguel; MARIKA KAAKINEN; VG Lyssenko; R Watanabe; E Ingelsson; Jose C Florez; J Dupuis; I Barroso; AP Morris; INGA PROKOPENKO

doi:10.1038/s41467-020-19366-9

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

Journal article

Peer reviewed

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

V Lagou, Reedik Magi, JJ Hottenga, Harald Grallert, John R. Perry, Nabila Bouatia-Naji, Letizia Marullo, Denis Rybin, R Jansen, JL Min, …

Nature Communications, Vol.12, 24

05/01/2021

DOI: https://doi.org/10.1038/s41467-020-19366-9

PMID: 33402679

Abstract

Adult

Anorexia Nervosa - blood

Anorexia Nervosa - ethnology

Anorexia Nervosa - genetics

Anorexia Nervosa - physiopathology

Blood Glucose - metabolism

European Continental Ancestry Group

Fasting - blood

Female

Genetic Loci

Genome-Wide Association Study

Glucose Intolerance - blood

Glucose Intolerance - ethnology

Glucose Intolerance - genetics

Glucose Intolerance - physiopathology

Humans

Insulin - blood

Insulin Receptor Substrate Proteins - blood

Insulin Receptor Substrate Proteins - genetics

Insulin Resistance - genetics

Kruppel-Like Transcription Factors - blood

Kruppel-Like Transcription Factors - genetics

Male

Middle Aged

Sex Characteristics

Sex Factors

Waist-Hip Ratio

Ethnic differences

Gene Expression

Phenotype

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.

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Title: Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability
Creators: V Lagou - VIB-KU Leuven Center for Brain and Disease Research, Leuven, Belgium
Reedik Magi - Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia
JJ Hottenga - Amsterdam Public Health Research Institute, VU University medical center, Amsterdam, the Netherlands
Harald Grallert - German Center for Diabetes Research (DZD, München-Neuherberg, Germany
John R. Perry - MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom
Nabila Bouatia-Naji - INSERM U970, Paris Cardiovascular Research Center PARCC, 75006, Paris, France
Letizia Marullo - Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy
Denis Rybin - Boston University Data Coordinating Center, Boston, MA, USA
R Jansen - Department of Psychiatry, VU University Medical Center, Amsterdam, the Netherlands
JL Min - Bristol Medical School, University of Bristol, Bristol, United Kingdom
AS Dimas - Institute for Bioinnovation, Biomedical Sciences Research Center Al. Fleming, Vari, Greece
ANNA ULRICH - Department of Medicine, Imperial College London, London, UK
LIUDMILA ZUDINA - Department of Medicine, Imperial College London, London, UK
Jesper R Gådin - Cardiovascular Medicine Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Karolinska University Hospital, Solna, Sweden
Longda Jiang - Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia
Alessia Faggian - Department of Medicine, Imperial College London, London, UK
Amélie Bonnefond - Department of Medicine, Imperial College London, London, UK
Joao Fadista - Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark
Maria G Stathopoulou - Université de Lorraine, IGE-PCV, F-54000, Nancy, France
Aaron Isaacs - Department of Physiology, Maastricht University, Maastricht, the Netherlands
SM Willems - Genetic Epidemiology Unit, Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands
Pau Navarro - MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK
T Tanaka - Translational Gerontology Branch, Longitudinal Study Section, National Institute on Aging, Baltimore, MD, USA
Anne U Jackson - Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA
May E Montasser - Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland, School of Medicine, Baltimore, MD, USA
Jeff R O'Connell - Division of Endocrinology, Diabetes, and Nutrition, Department of Medicine, University of Maryland, School of Medicine, Baltimore, MD, USA
Lawrence F Bielak - Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA
R. Webster - Laboratory for Cancer Medicine, Harry Perkins Institute of Medical Research, University of Western Australia Centre for Medical Research, Nedlands, WA, Australia
Richa Saxena - Departmentartment of Anesthesia, Critical Care and Pain Medicine, MGH, Boston, MA, USA
Jeanette M Stafford - Department of Biostatistics and Data Science, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA
Beate St Pourcain - Bristol Medical School, University of Bristol, Bristol, United Kingdom
Nicholas J. Timpson - Bristol Medical School, University of Bristol, Bristol, United Kingdom
Perttu Salo - Public Health Genomics Unit, Department of Chronic Disease Prevention, Finnish Institute for Health and Welfare, Helsinki, Finland
SY Shin - Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK
Najaf Amin - Department of Epidemiology Erasmus MC, Rotterdam, the Netherlands
Albert V Smith - Faculty of Medicine, University of Iceland, Reykjavik, Iceland
Guo Li - Department of Medicine, University of Washington, Seattle, WA, USA
Niek Verweij - Department of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
Anuj Goel - Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
Ian Ford - Robertson Centre for Biostatistics, University of Glasgow, Glasgow, UK
Paul C D Johnson - Institute of Biodiversity, Animal Health & Comparative Medicine, University of Glasgow, Glasgow, UK
T Johnson - NIHR Barts Cardiovascular Biomedical Research Unit, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
Karen Kapur - Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland
G Thorleifsson - deCODE Genetics, Reykjavik, Iceland
RJ Strawbridge - Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
Laura J Rasmussen-Torvik - Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL, USA
Tõnu Esko - Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia
Evelin Mihailov - Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia
T Fall - Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, Uppsala, Sweden
Ross M Fraser - Synpromics Ltd, Roslin Innovation Centre, Easter Bush Campus, Edinburgh, EH25 9RG, UK
A Mahajan - Genentech, 340 Point San Bruno Boulevard, South San Francisco, CA, 94080, USA
Stavroula Kanoni - Wellcome Trust Sanger Institute, Hinxton, UK
Vilmantas Giedraitis - Department of Public Health and Caring Sciences, Uppsala Universitet, Uppsala, Sweden
ME Kleber - Vth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany
Günther Silbernagel - Division of Angiology, Department of Internal Medicine, Medical University of Graz, Graz, Austria
Julia Meyer - Institute of Genetic Epidemiology,Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
Martina Müller-Nurasyid - Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI, University Medical Center, Johannes Gutenberg University, 55101, Mainz, Germany
Andrea Ganna - Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, MA, USA
Antti-Pekka Sarin - Public Health Genomics Unit, Finnish Institute for Health and Welfare, Helsinki, Finland
Loic Yengo - Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia
Dmitry Shungin - Department of Odontology, Umeå University, Umeå, Sweden
J Luan - MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom
Momoko Horikoshi - RIKEN, Center for Integrative Medical Sciences, Laboratory for Endocrinology, Metabolism and Kidney Disease, Yokohama, Japan
Ping An - Division of Statistical Genomics, Washington University School of Medicine, St. Louis, MO, USA
S Sanna - Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
Yvonne Boettcher - IFB AdiposityDiseases, University of Leipzig, Leipzig, Germany
NW Rayner - Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK
Ilja M Nolte - Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
Tatijana Zemunik - Faculty of Medicine, University of Split, Split, Croatia
Erik van Iperen - Department of Clinical Epidemiology and Biostatistics, Academic Medical Center, University of Amsterdam, Amsterdam, the Netherlands
Peter Kovacs - IFB AdiposityDiseases, University of Leipzig, Leipzig, Germany
Nicholas D Hastie - MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK
SH Wild - Usher Institute, University of Edinburgh, Edinburgh, UK
Stela McLachlan - Usher Institute, University of Edinburgh, Edinburgh, UK
SS Campbell - MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK
Ozren Polasek - Faculty of Medicine, University of Split, Split, Croatia
Olga Carlson - Laboratory of Clinical Investigation, National Institute of Aging, Baltimore, MD, USA
Josephine Egan - Laboratory of Clinical Investigation, National Institute of Aging, Baltimore, MD, USA
Wieland Kiess - Pediatric Research Center, Department of Women's & Child Health, University of Leipzig, Leipzig, Germany
G Willemsen - Department of Biological Psychology, Vrije Universiteit, Amsterdam, the Netherlands
Johanna Kuusisto - Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
Markku Laakso - Department of Medicine, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
Maria Dimitriou - Department of Dietetics-Nutrition, Harokopio University, Athens, Greece
A Hicks - Center for Biomedicine, European Academy Bozen/Bolzano (EURAC) (Affiliated Institute of the University of LübeckLübeckGermany), Bolzano, Italy
Rainer Rauramaa - Department of Clinical Physiology and Nuclear Medicine, Kuopio University Hospital, Kuopio, Finland
S Bandinelli - Geriatric Unit, Azienda Sanitaria Firenze (ASF), Florence, Italy
B Thorand - Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
Yongmei Liu - Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest University School of Medicine, Winston-Salem, NC, USA
Iva Miljkovic - Department of Epidemiology, Center for Aging and Population Health, University of Pittsburgh, Pittsburgh, PA, USA
L Lind - Department of Medical Sciences, Uppsala University, Akademiska sjukhuset, Uppsala, Sweden
Alex Doney - Pat McPherson Centre for Pharmacogenetics and Pharmacogenomics, Division of Molecular and Clinical Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
M Perola - Estonian Genome Center, University of Tartu, Tartu, Estonia
AD Hingorani - Department of Epidemiology and Public Health, University College London, London, UK
M Kivimäki - Department of Epidemiology and Public Health, University College London, London, UK
Meena Kumari - University of Essex, Wivenhoe Park, Colchester, Essex, UK
Amanda J Bennett - Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK
C Groves - Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK
C Herder - Division of Endocrinology and Diabetology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
Heikki A Koistinen - Minerva Foundation Institute for Medical Research, Biomedicum 2U, Tukholmankatu 8, Helsinki, FI-00290, Finland
Leena Kinnunen - Department of Public Health Solutions, Finnish Institute for Health and Welfare, P.O. Box 30, Helsinki, FI-00271, Finland
Ulf de Faire - Division of Cardiovascular Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
Stephan J L Bakker - Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
Matti Uusitupa - Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
Colin N. A Palmer - Pat McPherson Centre for Pharmacogenetics and Pharmacogenomics, Division of Molecular and Clinical Medicine, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
J Wouter Jukema - Netherlands Heart Institute, Utrecht, the Netherlands
N Sattar - Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom
A Pouta - PEDEGO Research Unit, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu, Finland
H Snieder - Department of Epidemiology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
E Boerwinkle - Division of Epidemiology, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX, USA
James S Pankow - Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MiI, USA
PK Magnusson - Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Ulrika Krus - Department of Clinical Sciences, Diabetes and Endocrinology Research Unit, University Hospital Malmö, Lund University, Malmö, Sweden
Chiara Scapoli - Department of Life Sciences and Biotechnology, University of Ferrara, Ferrara, Italy
Eco J C N de Geus - Amsterdam Public Health Research Institute, VU University medical center, Amsterdam, the Netherlands
Matthias Blüher - Department of Preventive Medicine, Keck School of Medicine of USC, Los Angeles, CA, USA
Bruce H R Wolffenbuttel - Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
Michael A Province - Division of Statistical Genomics, Washington University School of Medicine, St. Louis, MO, USA
G Abecasis - Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA
James B Meigs - Department of Medicine, Harvard Medical School, Boston, MA, USA
G Kees Hovingh - Novo Nordisk A/S, Copenhagen, Denmark
Jaana Lindström - Finnish Institute for Health and Welfare, Diabetes Prevention Unit, Helsinki, Finland
James F Wilson - Usher Institute, University of Edinburgh, Edinburgh, UK
Alan F Wright - MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK
GV Dedoussis - Department of Dietetics-Nutrition, Harokopio University, Athens, Greece
Stefan R Bornstein - Department of Medicine, Division for Prevention and Care of Diabetes, Faculty of Medicine Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany
Peter E H Schwarz - German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany
Anke Tönjes - IFB AdiposityDiseases, University of Leipzig, Leipzig, Germany
BR Winkelmann - Cardiology Group, Frankfurt-Sachsenhausen, Germany
B Boehm - Lee Kong Chian School of Medicine, Nanyang Technological University Singapore and Imperial College London, Singapore, Singapore
W März - Synlab Academy, Synlab Holding Deutschland GmbH, Mannheim, Germany
Andres Metspalu - Estonian Genome Centre, Institute of Genomics, University of Tartu, Tartu, Estonia
Jackie F Price - Usher Institute, University of Edinburgh, Edinburgh, UK
P Deloukas - Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders (PACER-HD, King Abdulaziz University, Jeddah, Saudi Arabia
Antje Körner - Diabetes Research Center, Diabetes Unit, Massachusetts General Hospital, Boston, MA, USA
Timo A. Lakka - Institute of Biomedicine/Physiology, University of Eastern Finland, Kuopio Campus, Kuopio, Finland
Sirkka M Keinanen-Kiukaanniemi - Unit of General Practice, Oulu University Hospital, Oulu, Finland
Timo E Saaristo - Pirkanmaa Hospital District, Tampere, Finland
Richard N Bergman - Diabetes and Obesity Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA, USA
J Tuomilehto - Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia
N Wareham - MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom
Claudia Langenberg - MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom
S Männistö - Department of Public Health Solutions, Finnish Institute for Health and Welfare, P.O. Box 30, Helsinki, FI-00271, Finland
Paul Franks - Department of Public Health & Clinical Medicine, Units of Medicine and Nutritional Research, Umeå University, Umeå, Sweden
C Hayward - MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK
Veronique Vitart - MRC Human Genetics Unit, MRC Institute of Genetics and Molecular Medicine, University of Edinburgh, Western General Hospital, Edinburgh, UK
J Kaprio - Department of Public Health, University of Helsinki, Helsinki, Finland
Sophie Visvikis-Siest - Université de Lorraine, IGE-PCV, F-54000, Nancy, France
Beverley Balkau - Univ Paris-Saclay, Univ Paris Sud, UVSQ, UMRS 1018, UMRS 1018, Villejuif, France
D Altshuler - Department of Medicine, Harvard Medical School, Boston, MA, USA
Igor Rudan - Usher Institute, University of Edinburgh, Edinburgh, UK
Michael Stumvoll - IFB AdiposityDiseases, University of Leipzig, Leipzig, Germany
Harry Campbell - Usher Institute, University of Edinburgh, Edinburgh, UK
Cornelia van Duijn - Centre for Medical Systems Biology, Leiden, the Netherlands
C Gieger - Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany
T Illig - Institute of Human Genetics, Hannover Medical School, Hannover, Germany
L Ferrucci - Clinical Research Branch, National Institute on Aging, Baltimore, Maryland, USA
NL Pedersen - Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
Peter P Pramstaller - Department of Neurology, University of Lübeck, Lübeck, Germany
Michael Boehnke - Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA
Timothy M. Frayling - Genetics of Complex Traits, Peninsula Medical School, University of Exeter, Exeter, UK
AR Shuldiner - The Regeneron Genetics Center, Regeneron Pharmaceuticals, Tarrytown, NY, USA
Patricia A Peyser - Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA
Sharon L R Kardia - Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI, USA
Lyle J. Palmer - School of Public Health, University of Adelaide, Adelaide, Australia
BW Penninx - Department of Psychiatry, VU University Medical Center, Amsterdam, the Netherlands
Pierre Meneton - U872 Institut National de la Santé et de la Recherche Médicale, Centre de Recherche des Cordeliers, 75006, Paris, France
T Harris - Geriatric Epidemiology Section, Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, MD, USA
G Navis - Department of Internal Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
Pim van der Harst - Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
George Davey Smith - MRC Integrative Epidemiology Unit (IEU), University of Bristol, Bristol, UK
NG Forouhi - MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Cambridge, United Kingdom
Ruth J F Loos - The Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
V Salomaa - Finnish Institute for Health and Welfare, Helsinki, Finland
N Soranzo - Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, UK
D Boomsma - Department of Biological Psychology, Vrije Universiteit, Amsterdam, the Netherlands
Leif Groop - Department of Clinical Sciences, Diabetes and Endocrinology Research Unit, University Hospital Malmö, Lund University, Malmö, Sweden
Tiinamaija Tuomi - Research Program for Clinical and Molecular Metabolism, University of Helsinki and Folkhälsan Research Center, Helsinki, Finland
Albert Hofman - Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, USA
Patricia B. Munroe - NIHR Barts Cardiovascular Biomedical Research Unit, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
V Gudnason - Faculty of Medicine University of Iceland, Reykjavik, Iceland
DS Siscovick - Department of Epidemiology, University of Washington, Seattle, WA, USA
H Watkins - Cardiovascular Medicine, Radcliffe Department of Medicine, University of Oxford, Oxford, UK
Cecile Lecoeur - CNRS UMR8199, Institut Pasteur de Lille, Lille, France
P Vollenweider - Department of Medicine, University Hospital Lausanne, Lausanne, Switzerland
A Franco-Cereceda - Cardiothoracic Surgery Unit, Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden
P Eriksson - Cardiovascular Medicine Unit, Center for Molecular Medicine, Department of Medicine, Karolinska Institutet, Stockholm, Karolinska University Hospital, Solna, Sweden
Marjo-Riitta Jarvelin - Institue of Health Sciences, University of Oulu, Oulu, Finland
K Stefansson - Faculty of Medicine, University of Iceland, Reykjavík, Iceland
A Hamsten - Department of Cardiology, Karolinska University Hospital Solna, Stockholm, Sweden
G Nicholson - Department of Statistics, University of Oxford, Oxford, UK
Fredrik Karpe - Oxford National Institute for Health Research Biomedical Research Centre, Churchill Hospital, Oxford, UK
ET Dermitzakis - Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland
C Lindgren - Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford, UK
MI McCarthy - Genentech, 340 Point San Bruno Boulevard, South San Francisco, CA, 94080, USA
P Froguel - Department of Medicine, Imperial College London, London, UK
MARIKA KAAKINEN - School of Biosciences and Medicine, Department of Clinical and Experimental Medicine, University of Surrey, Guildford, UK
VG Lyssenko - Department of Clinical Science, University of Bergen, Bergen, Norway
R Watanabe - USC Diabetes and Obesity Research Institute, Los Angeles, CA, USA
E Ingelsson - Stanford Cardiovascular Institute, Stanford University, Stanford, CA, 94305, USA
Jose C Florez - Diabetes Research Center, Diabetes Unit, Massachusetts General Hospital, Boston, MA, USA
J Dupuis - Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA
I Barroso - Exeter Centre of ExcEllence in Diabetes (ExCEED), University of Exeter Medical School, Exeter, UK
AP Morris - Centre for Genetics and Genomics Versus Arthritis, Centre for Musculoskeletal Research, The University of Manchester, Manchester, UK
INGA PROKOPENKO
Publication Details: Nature Communications, Vol.12, 24
Publisher: Nature Research
Date published: 05/01/2021
Date accepted: 22/09/2020
Grants: IEC\R2\181075, Royal Society of Medicine (United Kingdom, London) - RSM
2017/1641, World Cancer Research Fund International (United Kingdom, London)
2017/1641, World Cancer Research Fund UK (United Kingdom, London) - WCRF UK
Dynamic longitudinal exposome trajectories in cardiovascular and metabolic non-communicable diseases, 874739, European Commission (Belgium, Brussels) - EC
Grant note: The participating studies were supported by the following grants: Academy of Finland (129293, 117844, 40758, 211497, 118590, 102318, 123885, 77299, 124243, 136895, 141005, 129322, 104781, 120315, 129269, 1114194); ADA (7-08-MN-OK); BBSRC (G20234); BHF (PG/07/133/24260); Clinical Translational Science Institute (UL1RR033176); Croatian Ministry of Science (216-1080315-0302); Directorate C - Public Health and Risk Assessment, Health & Consumer Protection (2004310); Dutch Kidney Foundation (E033); Estonian Research Council (IUT20-60, IUT24-6, PUT1660); ERC: (284167, 771057, 230374, GENETARGET-T2D, GA 269045); European Regional Development Fund [2014-2020.4.01.15-0012 GENTRANSMED]; EU grants (HEALTH-F2-2009-223004, HEALTH-F4-2007-201413, HEALTH-F2-2013-601456, HEALTH-F2-2008-201865, 201668, 602768, 201413, 245536, LSHM CT 2006 037697, LSHM-CT- 2007-037273, LSHM-CT-2004-503485, LSHM-CT-2004-005272, LSHG-CT-2006-018947, LSHGCT-2004-512066, QLG2-CT-2002-01254, EU/QLRT-2001-01254; QLG1-CT-2000-01643, European Union Horizon 2020 [692145]); Federal Ministry of Education and Research (BMBF), Germany (FKZ: 01EO1501); Finnish Funding Agency for Technology and Innovation (40058/07); German Research Foundation (SFB-1052 “Obesity mechanisms” A01, B03, SPP 1629 TO 718/2- 1, B01, C05); Greek General Secretary of Research and Technology (PENED 2003); Icelandic National Bioethics Committee (VSN: 00-063); IFB Adiposity Diseases (AD2-060E, AD2-06E95, AD2-06E99); IngaBritt och Arne Lundberg’s Research Foundation (359); Italian Ministry of Health (ICS110.1/RF97.71); Knut & Alice Wallenberg foundation (KAW 2009.0243); Kuopio University Hospital from Ministry of Health and Social Affairs (5254); Affymetrix, Inc for genotyping services (Contract No. N02-HL-6-4278); Lundberg Foundation (359); Medical Research Council, UK (G0500539, G0600705); Mid-Atlantic Nutrition Obesity Research Center (P30 DK072488); Ministry of Education and Culture of Finland (627;2004-2011); MRC-GSK pilot programme (ID 85374); NHLBI (HL054457, HL054464, HL054481, HL119443, HL087660, HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, N01-HC-85239, N01-HC-85079 through N01-HC-85086, N01-HC-35129, N01 HC-15103, N01 HC-55222, N01-HC-75150, N01-HC-45133, HL36310, U01 HG004171, N01-HC-25195, HHSN268201500001I, HL080295, HL075366, HL087652, HL105756, 5R01HL087679-02); NIA (NO1-AG-1-2109, N01AG62101, N01AG62103, N01AG62106, 1R01AG032098-01A1, AG-023629, AG-15928, AG-20098, AG-027058, AG13196, N01-AG-5-0002, 263 MD 9164, 263 MD 821336, N.1-AG-1-1, N.1-AG-1-2111); NIH (N01-AG-1-2100 and HHSN271201200022C, HHSN268200782096C, HHSN268200625226C, AG028555, AG08724, AG04563, AG10175, AG08861, U01 DK062370, R01-HG000376, R01-DK072193, ZIA HG000024, N01-HG-65403, R01 088119, R01 AR046838, U01 HL72515, R01 AG18728, R01HL087641, R01HL59367, R01HL086694, U01HG004402, UL1RR025005, 5R01HL08770003, 5R01HL08821502, 5R01DK07568102, 5R01DK06833603, DK063491, DK U01-066134, LM010098, 1K08AR055688, R01 DK078616, NIDDK K24 DK080140, 1RL1MH083268-01, 5R01MH63706:02, R01 [MP1GV17428], HS06516, M01 RR 16500), R01D0042157-01A1, R01MH58799-03, MH081802, DA018673, R01 DK092127-04, 1RC2 MH089951, 1RC2 MH089995; Nordic Centre of Excellence on Systems biology in controlled dietary interventions and cohort studies, SYSDIET (070014); Novo Nordisk Foundation’s (NNF15CC0018486); NWO/ZonMW (175.010.2007.006, 916.761.70, 10-000-1002, 2018/EW/00408559, 904-61-090, 985-10-002, 912-10-020, 904-61-193, 480-04-004, 463-06-001, 451-04-034, 400-05-717, Addiction-31160008, 016-115-035, 481-08-011, 400-07-080, 056-32-010, Middelgroot-911-09-032, OCW_NWO Gravity program –024.001.003, NWO-Groot 480-15-001/674, NBIC/BioAssist/RK(2008.024), BBMRI –NL, 184.021.007 and 184.033.111); Spinozapremie (NWO- 56-464-14192)); Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06); Stockholm County Council (592229, 560283); Swedish Foundation for Strategic Research (ICA08-0047); Swedish Heart-Lung Foundation (201202729); Swedish Research Council (8691, 0593, M-2005-1112, 2009-2298, 521-2010-3490, 521-2010-3490, 521-2010-3490, 521-2007-4037, 521-2008-2974, 349 2006-237P, 12660, 521-2010-2633, 521-2010-3490); Swiss National Science Foundation (3200B0–105993, 3200B0-118308, 33CSCO-122661, 33CS30-139468, 33CS30-148401); TEKES (70103/06, 40058/07); Torsten och Ragnar Söderbergs Stiftelser (MT33/09); Wellcome Trust (WT098051, 084727/Z/08/Z, 085475/Z/08/Z, 085475/B/08/Z, 090532/Z/09/Z, 203141/Z/16/Z, 201543/B/16/Z, 092447/Z/10/Z, 217065/Z/19/Z, 090532, 098381, 083948, GR069224); Yrjö Jahnsson Foundation (56358).). Individual acknowledgements A.P.M. is a Wellcome Trust Senior Fellow in Basic Biomedical Science (grant number WT098017). A.R.S. is an employee of Regeneron Pharmaceuticals ALE was supported as a research fellow by the Sarnoff Cardiovascular Research Fellowship. A.S.D. acknowledges support by the Stavros Niarchos Foundation. A.V.S. acknowledges support from the American Diabetes Association (Award No.: 7-08-MN-OK). C. Hayward and V.V. are supported by an MRC University Unit Programme Grant MC_UU_00007/10 (QTL in Health and Disease). C.M.L. is supported by the Li Ka Shing Foundation, WT-SSI/John Fell funds and by the NIHR Biomedical Research Centre, Oxford, by Widenlife and NIH (5P50HD028138-27). D.A. acknowledges support from US National Institutes of Health/National Heart, Lung, and Blood Institute grant (U01 HG004171). D.A. was a Burroughs Wellcome Fund Clinical Scholar in Translational Research and is a Distinguished Clinical Scholar of the Doris Duke Charitable Foundation. D.A. acknowledges sponsored research funding from Pfizer, Inc. S.R. is supported by an NIH Career Development Award (1K08AR055688). E.T.D. was funded by the Swiss National Science Foundation, Louis-Jeantet Foundation. H.W. is supported by the British Heart Foundation Centre for Research Excellence. G.D.S.: MC_UU_00011-1. I.B. acknowledges funding from the Wellcome Trust grant 098051, United Kingdom NIHR Cambridge Biomedical Research Centre and the MRC Centre for Obesity and Related Metabolic Diseases. I.P. is funded by the World Cancer Research Fund (WCRF UK) and World Cancer Research Fund International (2017/1641), the Wellcome Trust (WT205915), the European Union’s Horizon 2020 research and innovation program (DYNAhealth, H2020-PHC-2014-633595, LONGITOOLS, H2020-SC1-2019-874739, the Ministry of Science and Higher Education of Russian Federation (2020-220-08-2197), the ANR, French National Agency for Research (PreciDIAB, reference: ANR-18-IBHU-0001) and the Royal Society (IEC\R2\181075). J. Kaprio acknowledges support by the Academy of Finland (grants 308248, 312073). J.M.: U01 DK078616, K24 DK080140. J.P., A.G. and H.W. acknowledge support from the Wellcome Trust, European Union Seventh Framework Programme FP7/2007-2013 under grant agreement no. HEALTH-F2-2013-601456 (CVGenes@Target) & the TriPartite Immunometabolism Consortium [TrIC]-Novo Nordisk Foundation’s Grant number NNF15CC0018486. M.A.K. is funded by the LONGITOOLS, H2020-SC1-2019-874739. M.I.M. was a Wellcome Senior Investigator and an NIHR Senior Investigator. Analytical work was supported by the Wellcome Trust (Grants nos. 090532, 106130, 098381, 203141, 212259); Medical Research Council grant no. MR/L020149/1; NIDDK (U01-DK105535, R01-MH101814, R01-MH090941); NIHR (NF-SI-0617-10090). P.B.M. wishes to acknowledge the support of the NIHR Cardiovascular Biomedical Research Unit at Barts and Queen Mary University of London, UK. R.M. was supported by Estonian Research Council grant PUT PRG687 and institutional grant PP1GI19935 from Institute of Genomics, University of Tartu. S.Männistö was supported by Academy of Finland (# 136895 and 141005). V.L. was supported by a fellowship from the Research Foundation – Flanders (FWO). V.S. has been supported by the Finnish Foundation for Cardiovascular Research.
Identifiers: 99594523802346
Copyright: © The Author(s) 2021, corrected publication 2021. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/ licenses/by/4.0/.
Academic Unit: School of Biosciences
Language: English
Resource Type: Journal article
SDG (Scopus 2023): SDG 3

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

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