A genomic approach to therapeutic target validation identifies a glucose-lowering <i>GLP1R</i> variant protective for coronary heart disease
-
- 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>
収録刊行物
-
- Science Translational Medicine
-
Science Translational Medicine 8 (341), 341ra76-, 2016-06
American Association for the Advancement of Science (AAAS)
- Tweet
キーワード
詳細情報 詳細情報について
-
- CRID
- 1362262943987781248
-
- ISSN
- 19466242
- 19466234
-
- データソース種別
-
- Crossref