A genomic approach to therapeutic target validation identifies a glucose-lowering <i>GLP1R</i> variant protective for coronary heart disease

DOI Web Site 被引用文献3件
  • Robert A. Scott
    Medical Research Council (MRC) Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
  • Daniel F. Freitag
    Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, Cambridge CB1 8RN, UK.
  • Li Li
    Statistical Genetics, Projects, Clinical Platforms, and Sciences (PCPS), GlaxoSmithKline, Research Triangle Park, NC 27709, USA.
  • Audrey Y. Chu
    Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, MA 02115, USA.
  • Praveen Surendran
    Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, Cambridge CB1 8RN, UK.
  • Robin Young
    Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, Cambridge CB1 8RN, UK.
  • Niels Grarup
    The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
  • Alena Stancáková
    Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, FI-70211 Kuopio, Finland.
  • Yuning Chen
    Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA.
  • Tibor V. Varga
    Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, SE-205 Malmö, Sweden.
  • Hanieh Yaghootkar
    Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter EX1 2LU, UK.
  • Jian’an Luan
    Medical Research Council (MRC) Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
  • Jing Hua Zhao
    Medical Research Council (MRC) Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
  • Sara M. Willems
    Medical Research Council (MRC) Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
  • Jennifer Wessel
    Department of Epidemiology, Fairbanks School of Public Health, Indianapolis, IN 46202, USA.
  • Shuai Wang
    Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA.
  • Nisa Maruthur
    Division of General Internal Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
  • Kyriaki Michailidou
    Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Laboratory, Worts Causeway, Cambridge CB1 8RN, UK.
  • Ailith Pirie
    Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Laboratory, Worts Causeway, Cambridge CB1 8RN, UK.
  • Sven J. van der Lee
    Department of Epidemiology, Erasmus University Medical Center, 3000 CA Rotterdam, Netherlands.
  • Christopher Gillson
    Medical Research Council (MRC) Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
  • Ali Amin Al Olama
    Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Laboratory, Worts Causeway, Cambridge CB1 8RN, UK.
  • Philippe Amouyel
    University of Lille, INSERM, Centre Hospitalier Régional Universitaire de Lille, Institut Pasteur de Lille, UMR 1167, RID-AGE, F-59000 Lille, France.
  • Larraitz Arriola
    Public Health Division of Gipuzkoa, San Sebastian 20013, Spain.
  • Dominique Arveiler
    Department of Epidemiology and Public Health (EA3430), University of Strasbourg, 67085 Strasbourg, France.
  • Iciar Aviles-Olmos
    Sobell Department of Motor Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK.
  • Beverley Balkau
    INSERM, Centre de Recherche en Epidémiologie et Santé des Populations (CESP), 94807 Villejuif, France.
  • Aurelio Barricarte
    CIBER Epidemiología y Salud Pública (CIBERESP), Madrid 28029, Spain.
  • Inês Barroso
    The Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.
  • Sara Benlloch Garcia
    Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Laboratory, Worts Causeway, Cambridge CB1 8RN, UK.
  • Joshua C. Bis
    Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA 98101, USA.
  • Stefan Blankenberg
    Department of General and Interventional Cardiology, University Heart Center Hamburg, 20246 Hamburg, Germany.
  • Michael Boehnke
    Department of Biostatistics and Center for Statistical Genetics, University of Michigan, Ann Arbor, MI 48109–2029, USA.
  • Heiner Boeing
    German Institute of Human Nutrition, Potsdam-Rehbruecke, 14558 Nuthetal, Germany.
  • Eric Boerwinkle
    Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, Houston, TX 77025, USA.
  • Ingrid B. Borecki
    Department of Genetics, Division of Statistical Genomics, Washington University School of Medicine, St. Louis, MO 63108, USA.
  • Jette Bork-Jensen
    The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
  • Sarah Bowden
    Cancer Research UK Clinical Trials Unit, Institute for Cancer Studies, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
  • Carlos Caldas
    Cancer Research UK Cambridge Institute and Department of Oncology, Li Ka Shing Centre, University of Cambridge, Cambridge CB2 0RE, UK.
  • Muriel Caslake
    University of Glasgow, Glasgow G12 8QQ, UK.
  • L. Adrienne Cupples
    Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA.
  • Carlos Cruchaga
    Department of Psychiatry, Washington University School of Medicine, St. Louis, MO 63110, USA.
  • Jacek Czajkowski
    Division of Statistical Genomics, Department of Genetics and Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63108, USA.
  • Marcel den Hoed
    Department of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, SE-752 37 Uppsala, Sweden.
  • Janet A. Dunn
    Warwick Clinical Trials Unit, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK.
  • Helena M. Earl
    University of Cambridge and National Institute of Health Research Cambridge Biomedical Research Centre, Cambridge University Hospitals National Health Service Foundation Trust, Cambridge CB2 0QQ, UK.
  • Georg B. Ehret
    McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, MD 21205, USA.
  • Ele Ferrannini
    Consiglio Nazionale delle Ricerche (CNR), Institute of Clinical Physiology, 56124 Pisa, Italy.
  • Jean Ferrieres
    Department of Epidemiology, UMR 1027, INSERM, Centre Hospitalier Universitaire (CHU) de Toulouse, 31000 Toulouse, France.
  • Thomas Foltynie
    Sobell Department of Motor Neuroscience, UCL Institute of Neurology, London WC1N 3BG, UK.
  • Ian Ford
    University of Glasgow, Glasgow G12 8QQ, UK.
  • Nita G. Forouhi
    Medical Research Council (MRC) Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
  • Francesco Gianfagna
    Department of Clinical and Experimental Medicine, Research Centre in Epidemiology and Preventive Medicine, University of Insubria, 21100 Varese, Italy.
  • Carlos Gonzalez
    Catalan Institute of Oncology (ICO), Barcelona 08908, Spain.
  • Sara Grioni
    Epidemiology and Prevention Unit, 20133 Milan, Italy.
  • Louise Hiller
    Warwick Clinical Trials Unit, University of Warwick, Gibbet Hill Road, Coventry CV4 7AL, UK.
  • Jan-Håkan Jansson
    Research Unit, 931 41 Skellefteå, Sweden.
  • Marit E. Jørgensen
    Steno Diabetes Center, 2820 Gentofte, Denmark.
  • J. Wouter Jukema
    Leiden University Medical Center, 2333 ZA Leiden, Netherlands.
  • Rudolf Kaaks
    German Cancer Research Centre (DKFZ), 69120 Heidelberg, Germany.
  • Frank Kee
    UK Clinical Research Collaboration (UKCRC) Centre of Excellence for Public Health, Queen’s University Belfast, Northern Ireland, Belfast BT12 6BJ, UK.
  • Nicola D. Kerrison
    Medical Research Council (MRC) Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
  • Timothy J. Key
    University of Oxford, Oxford OX1 2JD, UK.
  • Jukka Kontto
    National Institute for Health and Welfare, FI-00271 Helsinki, Finland.
  • Zsofia Kote-Jarai
    The Institute of Cancer Research, London SM2 5NG, UK.
  • Aldi T. Kraja
    Division of Statistical Genomics, Department of Genetics and Center for Genome Sciences and Systems Biology, Washington University School of Medicine, St. Louis, MO 63108, USA.
  • Kari Kuulasmaa
    National Institute for Health and Welfare, FI-00271 Helsinki, Finland.
  • Johanna Kuusisto
    Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, FI-70211 Kuopio, Finland.
  • Allan Linneberg
    Research Centre for Prevention and Health, Capital Region, DK-2600 Copenhagen, Denmark.
  • Chunyu Liu
    Framingham Heart Study, Population Sciences Branch, NHLBI/National Institutes of Health (NIH), Bethesda, MD 20892, USA.
  • Gaëlle Marenne
    The Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.
  • Karen L. Mohlke
    Department of Genetics, University of North Carolina, Chapel Hill, NC 27599–7264, USA.
  • Andrew P. Morris
    Department of Biostatistics, University of Liverpool, Liverpool L69 3GL, UK.
  • Kenneth Muir
    Centre for Epidemiology, Institute of Population Health, University of Manchester, Oxford Road, Manchester M13 9PT, UK.
  • Martina Müller-Nurasyid
    Institute of Genetic Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, D-85764 Neuherberg, Germany.
  • Patricia B. Munroe
    Clinical Pharmacology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
  • Carmen Navarro
    CIBER Epidemiología y Salud Pública (CIBERESP), Madrid 28029, Spain.
  • Sune F. Nielsen
    Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, University of Copenhagen, 2730 Copenhagen, Denmark.
  • Peter M. Nilsson
    Lund University, 20502 Malmö, Sweden.
  • Børge G. Nordestgaard
    Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, University of Copenhagen, 2730 Copenhagen, Denmark.
  • Chris J. Packard
    University of Glasgow, Glasgow G12 8QQ, UK.
  • Domenico Palli
    Cancer Research and Prevention Institute (ISPO), 50141 Florence, Italy.
  • Salvatore Panico
    Dipartimento di Medicina Clinica e Chirurgia, Federico II University, 80131 Naples, Italy.
  • Gina M. Peloso
    Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Markus Perola
    National Institute for Health and Welfare, FI-00271 Helsinki, Finland.
  • Annette Peters
    DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, 80802 Munich, Germany.
  • Christopher J. Poole
    University of Warwick, Coventry CV4 7AL, UK.
  • J. Ramón Quirós
    Public Health Directorate, 33006 Oviedo, Asturias, Spain.
  • Olov Rolandsson
    Umeå University, 90187 Umeå, Sweden.
  • Carlotta Sacerdote
    Unit of Cancer Epidemiology, Citta’ della Salute e della Scienza Hospital, University of Turin, 10126 Torino, Italy.
  • Veikko Salomaa
    National Institute for Health and Welfare, FI-00271 Helsinki, Finland.
  • María-José Sánchez
    CIBER Epidemiología y Salud Pública (CIBERESP), Madrid 28029, Spain.
  • Naveed Sattar
    University of Glasgow, Glasgow G12 8QQ, UK.
  • Stephen J. Sharp
    Medical Research Council (MRC) Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
  • Rebecca Sims
    Institute of Psychological Medicine and Clinical Neuroscience, MRC Centre, Cardiff University, Cardiff CF24 4HQ, UK.
  • Nadia Slimani
    International Agency for Research on Cancer, 69372 Lyon, France.
  • Jennifer A. Smith
    Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109–2029, USA.
  • Deborah J. Thompson
    Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Laboratory, Worts Causeway, Cambridge CB1 8RN, UK.
  • Stella Trompet
    Leiden University Medical Center, 2333 ZA Leiden, Netherlands.
  • Rosario Tumino
    Cancer Registry and Histopathology Unit, “Civic–M.P. Arezzo” Hospital, ASP Ragusa, 97100 Ragusa, Italy.
  • Daphne L. van der A
    National Institute for Public Health and the Environment (RIVM), 3720 BA Bilthoven, Netherlands.
  • Yvonne T. van der Schouw
    University Medical Center Utrecht, 3508 GA Utrecht, Netherlands.
  • Jarmo Virtamo
    National Institute for Health and Welfare, FI-00271 Helsinki, Finland.
  • Mark Walker
    Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne NE2 4HH, UK.
  • Klaudia Walter
    The Wellcome Trust Sanger Institute, Cambridge CB10 1SA, UK.
  • Jean E. Abraham
    Centre for Cancer Genetic Epidemiology, Department of Oncology, University of Cambridge, Strangeways Laboratory, Worts Causeway, Cambridge CB1 8RN, UK.
  • Laufey T. Amundadottir
    Laboratory of Translational Genomics, Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
  • Jennifer L. Aponte
    Genetics, PCPS, GlaxoSmithKline, Research Triangle Park, NC 27709, USA.
  • Adam S. Butterworth
    Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, Cambridge CB1 8RN, UK.
  • Josée Dupuis
    Department of Biostatistics, Boston University School of Public Health, Boston, MA 02118, USA.
  • Douglas F. Easton
    Centre for Cancer Genetic Epidemiology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Laboratory, Worts Causeway, Cambridge CB1 8RN, UK.
  • Rosalind A. Eeles
    The Institute of Cancer Research, London SM2 5NG, UK.
  • Jeanette Erdmann
    Institut für Integrative und Experimentelle Genomik, Universität zu Lübeck, 23562 Lübeck, Germany.
  • Paul W. Franks
    Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University, SE-205 Malmö, Sweden.
  • Timothy M. Frayling
    Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter EX1 2LU, UK.
  • Torben Hansen
    The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
  • Joanna M. M. Howson
    Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, Cambridge CB1 8RN, UK.
  • Torben Jørgensen
    Research Centre for Prevention and Health, DK-2600 Capital Region, Denmark.
  • Jaspal Kooner
    National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK.
  • Markku Laakso
    Department of Medicine, University of Kuopio, FI-70211 Kuopio, Finland.
  • Claudia Langenberg
    Medical Research Council (MRC) Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
  • Mark I. McCarthy
    Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.
  • James S. Pankow
    Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN 55455–0381, USA.
  • Oluf Pedersen
    The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, 2200 Copenhagen, Denmark.
  • Elio Riboli
    School of Public Health, Imperial College London, London W2 1PG, UK.
  • Jerome I. Rotter
    Institute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor–University of California, Los Angeles Medical Center, Torrance, CA 90502, USA.
  • Danish Saleheen
    Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, PA 19104, USA.
  • Nilesh J. Samani
    Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester LE3 9QP, UK.
  • Heribert Schunkert
    DZHK (German Centre for Cardiovascular Research), partner site Munich Heart Alliance, 80802 Munich, Germany.
  • Peter Vollenweider
    Department of Internal Medicine, BH10-462, Internal Medicine, Lausanne University Hospital (CHUV), CH-1011 Lausanne, Switzerland.
  • Stephen O’Rahilly
    University of Cambridge Metabolic Research Laboratories, Wellcome Trust–MRC Institute of Metabolic Science, Cambridge CB2 0QQ, UK.
  • Panos Deloukas
    William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London EC1M 6BQ, UK.
  • John Danesh
    Department of Public Health and Primary Care, Strangeways Research Laboratory, University of Cambridge, Cambridge CB1 8RN, UK.
  • Mark O. Goodarzi
    Division of Endocrinology, Diabetes and Metabolism, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA.
  • Sekar Kathiresan
    Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA 02114, USA.
  • James B. Meigs
    Division of General Internal Medicine, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Margaret G. Ehm
    Genetics, PCPS, GlaxoSmithKline, Research Triangle Park, NC 27709, USA.
  • Nicholas J. Wareham
    Medical Research Council (MRC) Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge CB2 0QQ, UK.
  • Dawn M. Waterworth
    Genetics, PCPS, GlaxoSmithKline, Philadelphia, PA 19104, USA.

抄録

<jats:p>A missense variant in GLP1R associated with lower fasting glucose levels and protective against T2D is associated with lower risk of coronary heart disease, suggesting that GLP1R agonists are not associated with an unacceptable increase in cardiovascular risk.</jats:p>

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