Identification of heart rate–associated loci and their effects on cardiac conduction and rhythm disorders

Nature Genetics - Tập 45 Số 6 - Trang 621-631 - 2013
Marcel den Hoed1, Mark Eijgelsheim2, Tõnu Esko3, Bianca J.J.M. Brundel4, David Peal5, David M. Evans6, Ilja M. Nolte7, Ayellet V. Segrè8, Hilma Hólm9, Robert E. Handsaker10, Harm-Jan Westra11, Toby Johnson12, Aaron Isaacs2, Jian Yang13, Alicia Lundby14, Jing Zhao1, Young Jin Kim15, Min Jin Go15, Peter Almgren16, Murielle Bochud17, Salome Scholtens18, Marilyn C. Cornelis19, Daníel F. Guðbjartsson9, David Hadley20, Pim van der Harst21, Caroline Hayward22, Martin den Heijer23, Åsa Johansson24, Anne Jackson25, Zoltán Kutalik26, Jian’an Luan1, John P. Kemp6, Kati Kristiansson27, Claes Ladenvall16, Mattias Lorentzon28, May E. Montasser29, Omer T. Njajou30, Paul F. O’Reilly31, Sandosh Padmanabhan32, Beaté St Pourcain6, Marie‐Claude Vohl33, Perttu Salo27, Toshiko Tanaka34, Nicholas J. Timpson6, Véronique Vitart22, Lindsay L. Waite35, William Wheeler36, Weihua Zhang31, Harmen H. M. Draisma37, Mary F. Feitosa38, Kathleen F. Kerr39, Penelope A. Lind40, Reedik Mägi41, N. Charlotte Onland‐Moret42, Ci Song43, Michael N. Weedon44, Weijia Xie44, Loïc Yengo45, Albert Hofman35, Christine M. Albert46, Álvaro Alonso47, Dan E. Arking48, Paul I.W. de Bakker10, Beverley Balkau49, Cristina Barlassina50, Paola Benaglio26, Joshua C. Bis51, Nabila Bouatia‐Naji45, Søren Brage1, Stephen S. Rich52, Inês Barroso53, Mina K. Chung54, Dawood Darbar55, Christian Dina56, Marcus Dörr57, Paul Elliott31, Stephan B. Felix57, Krista Fischer58, Christian Fuchsberger25, Eco J. C. de Geus37, Philippe Goyette18, Vilmundur Guðnason59, Tamara B. Harris60, Anna-Liisa Hartikainen61, Aki S. Havulinna62, Susan R. Heckbert51, Andrew A. Hicks63, Suzanne Holewijn64, Femke Hoogstra‐Berends4, Jouke‐Jan Hottenga37, Majken K. Jensen19, Juhani Junttila65, Stefan Kääb66, Bart Kanon67, Shamika Ketkar38, Kay‐Tee Khaw68, Joshua W. Knowles69, Angrad S Kooner70, Jan A. Kors71, Meena Kumari72, Lili Milani58, Päivi Laiho73, Edward G. Lakatta74, Claudia Langenberg1, Maarten Leusink75, Yongmei Liu76, Robert Luben68, Kathryn L. Lunetta77, Stacey N. Lynch5, Marcello Ricardo Paulista Markus78, Pedro Marques‐Vidal79, Irene Espósito21, Wendy L. McArdle80, Steven A. McCarroll81, Sarah E. Medland14, Kathryn Miller31, Grant W. Montgomery82, Alanna C. Morrison83, Martina Müller‐Nurasyid66, Pau Navarro22, Mari Nelis19, Jeffrey R. O’Connell29, Christopher J O’Donnell84, Ken K. Ong1, Anne B. Newman85, Annette Peters86, Ozren Polašek87, Anneli Pouta61, Peter P. Pramstaller63, Bruce M. Psaty51, D. C. Rao88, Susan M. Ring80, Elizabeth J. Rossin14, Diana Rudan89, Serena Sanna90, Robert A. Scott1, Joban Sehmi70, Stephen J. Sharp1, Jordan T. Shin5, Andrew Singleton91, Nicole Soranzo13, Tim D. Spector92, Chip Stewart14, Heather M. Stringham93, Kirill V. Tarasov74, André G. Uitterlinden94, Liesbeth Vandenput28, Shih‐Jen Hwang84, John B. Whitfield95, Cisca Wijmenga11, Sarah H. Wild96, Gonneke Willemsen37, James F. Wilson96, Jacqueline R. Center94, Andrew Wong97, Quenna Wong39, Yalda Jamshidi92, Paavo Zitting98, Jolanda M.A. Boer99, Dorret I. Boomsma37, Ingrid B. Borecki38, Cornelia M. van Duijn100, Ulf Ekelund101, Nita G. Forouhi1, Philippe Froguel45, Aroon D. Hingorani72, Erik Ingelsson43, Mika Kivimäki72, Richard A. Kronmal39, Diana Kuh97, Lars Lind102, Nicholas G. Martin95, Mark I. McCarthy103, Nancy L. Pedersen43, Thomas Quertermous69, Jerome I. Rotter104, Yvonne T. van der Schouw75, W. M. Monique Verschuren99, Mark Walker105, Demetrius Albanes52, Davíð O. Arnar106, Themistocles L. Assimes69, Stefania Bandinelli107, Michael Boehnke93, Rudolf A. de Boer21, Claude Bouchard33, Wilson Caulfield108, John C. Chambers31, Gary C. Curhan109, Daniele Cusi50, Johan G. Eriksson62, Luigi Ferrucci34, Wiek H. van Gilst21, Nicola Glorioso110, Jacqueline de Graaf64, Leif Groop16, Ulf Gyllensten24, Wen-Chi Hsueh30, Frank B. Hu19, Heikki V. Huikuri111, David J. Hunter112, Carlos Iribarren113, Bo Isomaa114, Marjo‐Riitta Järvelin115, Antti Jula116, Mika Kähönen117, Lambertus A. Kiemeney118, Melanie M. van der Klauw119, Jaspal S. Kooner70, Peter Kraft112, Licia Iacoviello120, Terho Lehtimäki117, Marja‐Liisa Lokki121, Braxton D. Mitchell29, Gerjan Navis122, Markku S. Nieminen123, Claes Ohlsson28, Neil Poulter124, Lu Qi19, Olli T. Raitakari125, Eric B. Rimm19, John D. Rioux126, Federica Rizzi127, Igor Rudan96, Veikko Salomaa62, Peter Sever124, Denis C. Shields128, Alan R. Shuldiner29, Juha Sinisalo123, Alice Stanton129, Ronald P. Stolk7, David P. Strachan20, Jean‐Claude Tardif126, Unnur Þorsteinsdóttir130, J. Tuomilehto131, Dirk J. van Veldhuisen21, Jarmo Virtamo62, Jorma Viikari132, Péter Vollenweider133, Gérard Waeber133, Elisabeth Widén134, Yoon Shin Cho135, Jesper V. Olsen136, Peter M. Visscher137, Cristen J. Willer138, Lude Franke139, Jeanette Erdmann63, J. Thompson140, Arne Pfeufer141, Nona Sotoodehnia51, Christopher Newton‐Cheh84, Patrick T. Ellinor142, Bruno H. Stricker71, Andres Metspalu41, Markus Perola62, J. Beckmann143, George Davey Smith6, Kāri Stefánsson130, Patricia B. Munroe108, Ody C. M. Sibon67, David J. Milan144, Harold Snieder7, Nilesh J. Samani145, Ruth J. F. Loos146
1Medical Research Council (MRC) Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, UK
2Department of Epidemiology, Erasmus University Medical Center, Rotterdam, the Netherlands
3Estonian Biocenter, Tartu, Estonia
4Department of Clinical Pharmacology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
5Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA
6MRC Centre for Causal Analyses in Translational Epidemiology (CAiTE), School of Social and Community Medicine, University of Bristol, Bristol, UK
7Department of Epidemiology, University Medical Center Groningen, University of Groningen, Groningen The Netherlands
8Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA
9deCODE Genetics, Reykjavik, Iceland
10Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, Massachusetts, USA
11Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
12Clinical Pharmacology, National Institute for Health Research (NIHR) Cardiovascular Biomedical Research Unit, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK
13Wellcome Trust Sanger Institute, Hinxton, Cambridge, UK
14Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA
15Center for Genome Science, National Institute of Health, Osong Health Technology Administration Complex, Daejeon, Republic of Korea
16Department of Clinical Sciences, Diabetes and Endocrinology, Lund University and Lund University Diabetes Centre, Malmö, Sweden
17Community Prevention Unit, Institute of Social and Preventive Medicine, Lausanne University Hospital, Lausanne, Switzerland
18Université de Montréal, Montreal, Quebec, Canada.
19Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA
20Division of Population Health Sciences and Education, St George’s, University of London, London, UK
21Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
22MRC Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK
23Department of Internal Medicine, VU Medical Center, Amsterdam, The Netherlands
24Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden
25Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA
26Department of Medical Genetics, University of Lausanne, Lausanne, Switzerland
27The Institute of Molecular Medicine, University of Helsinki, Helsinki, Finland
28Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
29Department of Medicine, Division of Endocrinology, Diabetes and Nutrition, University of Maryland, School of Medicine, Baltimore, Maryland, USA
30Department of Medicine, Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA
31Department of Epidemiology and Biostatistics, Imperial College London, London, UK
32Institute of Cardiovascular and Medical Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
33Human Genomics Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA
34Clinical Research Branch, National Institute on Aging, Baltimore, Maryland, USA
35HudsonAlpha Institute for Biotechnology, Huntsville, Alabama, USA
36Information Management Services, Inc Rockville, Maryland, USA
37Department of Biological Psychology, VU University Amsterdam and Institute for Health and Care Research (EMGO+), VU Medical Center, Amsterdam, The Netherlands
38Division of Statistical Genomics, Washington University School of Medicine, St. Louis, Missouri, USA
39Department of Biostatistics, University of Washington, Seattle, Washington, USA.
40Quantitative Genetics Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland, Australia
41Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia
42Department of Medical Genetics–de Bakker Group, Complex Genetics Section, University Medical Center Utrecht, Utrecht, The Netherlands
43Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden
44Peninsula College of Medicine and Dentistry, University of Exeter, Exeter, UK
45Centre National de la Recherche Scientifique (CNRS) Unité Mixte de Recherche (UMR) 8199, Institut Pasteur de Lille, Lille, France
46Division of Preventive Medicine, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts, USA
47Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, Minnesota, USA
48Department of Medicine, Division of Cardiology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA
49Institut National de la Santé et de la Recherche Médicale (INSERM), CESP Centre for Research in Epidemiology and Population Health, U1018, Epidemiology of Diabetes, Obesity and Chronic Kidney Disease over the Lifecourse, Villejuif, France
50Department of Health Sciences, Milan University and Filarete Foundation, Milan, Italy
51Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA
52Division of Cancer Epidemiology and Genetics, US National Cancer Institute, Bethesda, Maryland, USA
53National Human Genome Research Institute, US National Institutes of Health, Bethesda, Maryland, USA
54Department of Cardiovascular Medicine, Heart and Vascular Institute, Cleveland Clinic, Cleveland, Ohio, USA
55Department of Medicine, Vanderbilt University School of Medicine Nashville, Tennessee, USA
56INSERM U1087, CNRS U6291 and University of Nantes, l'Institut du Thorax, Nantes, France
57Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany
58Estonian Genome Center, University of Tartu, Tartu, Estonia
59Icelandic Heart Association Research Institute, Kopavogur, Iceland
60Laboratory for Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, Maryland, USA
61Department of Clinical Sciences/Obstetrics and Gynecology, University of Oulu, Oulu, Finland
62Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland
63Center for Biomedicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy (affiliated institute of the University of Lübeck).,
64Department of General Internal Medicine, Division of Vascular Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands
65Division of Cardiology, Miller School of Medicine, University of Miami, Miami, Florida, USA
66Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians- Universität, Munich, Germany
67Department of Cell Biology, University Medical Center Groningen; University of Groningen, Groningen, The Netherlands
68Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge, Cambridge, UK
69Department of Medicine, Stanford University School of Medicine, Stanford, California USA
70Cardiology Department, Ealing Hospital National Health Service (NHS) Trust, London, UK
71Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, the Netherlands
72Department of Epidemiology and Public Health, Genetic Epidemiology Group, University College London, London, UK
73National Public Health Institute, Biomedicum Helsinki, Helsinki, Finland
74Laboratory of Cardiovascular Science, National Institute on Aging, Baltimore, Maryland, USA
75Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
76Department of Epidemiology & Prevention, Division of Public Health Sciences, Wake Forest University, Winston-Salem, North Carolina, USA
77Department of Biostatistics, School of Public Health, Boston University, Boston, Massachusetts, USA
78Institute for Community Medicine, University Medicine Greifswald, Greifswald, Germany
79Institut Universitaire de Médecine Sociale et Préventive (IUMSP), Centre Hospitalier Universitaire Vaudois (CHUV) and University of Lausanne, Lausanne, Switzerland
80School of Social and Community Medicine, University of Bristol, Bristol, UK
81Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA
82Molecular Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland, Australia
83Human Genetics Center, University of Texas Health Science Center, Houston, Texas, USA
84National Heart, Lung, and Blood Institute’s Framingham Heart Study, Framingham, Massachusetts, USA.
85Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
86Munich Heart Alliance, Munich, Germany
87Department of Public Health, Faculty of Medicine, University of Split, Split, Croatia
88Division of Biostatistics, Washington University School of Medicine, St. Louis, Missouri, USA
89Department of Pathophysiology, Faculty of Medicine, University of Split, Split, Croatia
90Istituto di Ricerca Genetica e Biomedica, Consiglio Nazionale delle Ricerche (CNR), Monserrato, Italy
91Laboratory of Neurogenetics, National Institute on Aging, Bethesda, Maryland, USA
92Department of Twin Research and Genetic Epidemiology Unit, St. Thomas' Campus, King's College London, St. Thomas' Hospital, London, UK
93Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA
94Netherlands Genomics Initiative-Sponsored Netherlands Consortium for Healthy Ageing, Rotterdam, The Netherlands
95Genetic Epidemiology Laboratory, Queensland Institute of Medical Research, Brisbane, Queensland, Australia
96Centre for Population Health Sciences, University of Edinburgh, Edinburgh, UK
97MRC Unit for Lifelong Health and Ageing, London, UK
98Department of Physiatrics, Lapland Central Hospital, Rovaniemi, Finland
99Centre for Nutrition, Prevention and Health Services, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands
100Centre for Medical Systems Biology, Leiden, The Netherlands
101Department of Sports Medicine, Norwegian School of Sport Sciences, Oslo, Norway
102Department of Medical Sciences, Uppsala University, Akademiska sjukhuset, Uppsala, Sweden
103Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands
104Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA
105Institue of Cellular Medicine, Newcastle University, Newcastle, UK
106Department of Medicine, Landspitali University Hospital, Reykjavik, Iceland
107Geriatric Unit, Azienda Sanitaria Firenze (ASF), Florence, Italy
108Genome Centre, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
109Channing Laboratory and Renal Division, Brigham and Women's Hospital, Boston, Massachusetts, USA
110Hypertension and Related Diseases Centre–Azienda Ospedaliero Universitaria (AOU), University of Sassari, Sassari, Italy
111Department of Internal Medicine, Institute of Clinical Medicine, University of Oulu, Oulu, Finland
112Program in Molecular and Genetic Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA
113Division of Research, Kaiser Permanente of Northern California, Oakland, California, USA
114Folkhälsan Research Centre, Helsinki, Finland
115MRC–Health Protection Agency (MRC-HPA) Centre for Environment and Health, Imperial College London, London, UK
116Department of Chronic Disease Prevention, National Institute for Health and Welfare, Turku, Finland
117Department of Clinical Chemistry, University of Tampere and Tampere University Hospital, Tampere, Finland
118Department for Health Evidence, Radboud University Medical Centre, Nijmegen, The Netherlands
119Department of Endocrinology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands
120Laboratory of Genetic and Environmental Epidemiology, Fondazione di Ricerca e Cura Giovanni Paolo II, Catholic University, Campobasso, Italy
121Transplantation Laboratory, Haartman Institute, University of Helsinki, Helsinki, Finland
122Department of Internal Medicine, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
123Department of Medicine, Division of Cardiology, Helsinki University Central Hospital, Helsinki, Finland
124International Centre for Circulatory Health (ICCH), Imperial College London, London, UK
125Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku, Finland
126Montreal Heart Institute, Montreal, Quebec, Canada
127Kos Genetic, Milan, Italy
128Complex and Adaptive Systems Laboratory, University College Dublin, Belfield, Dublin, Ireland
129Molecular and Cellular Therapeutics, Royal College of Surgeons in Ireland, Dublin, Ireland
130Faculty of Medicine, University of Iceland, Reykjavik, Iceland
131Diabetes Unit, National Institute for Health and Welfare, Helsinki, Finland
132Department of Medicine, University of Turku and Turku University Hospital, Turku, Finland
133Department of Internal Medicine, University Hospital of Lausanne, Lausanne, Switzerland
134Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland
135Department of Biomedical Science, Hallym University, Chuncheon, Korea
136Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Copenhagen, Denmark
137Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia
138Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan, USA
139Blizard Institute of Cell and Molecular Science, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
140Department of Health Sciences, University of Leicester Leicester UK
141Institute of Human Genetics, Helmholtz Zentrum München–German Research Center for Environmental Health, Munich, Germany
142Harvard Medical School Boston Massachusetts USA
143Service of Medical Genetics, CHUV University Hospital, Lausanne, Switzerland
144Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, USA
145Department of Cardiovascular Sciences, University of Leicester, Glenfield Hospital, Leicester, UK
146The Genetics of Obesity and Related Metabolic Traits Program, The Icahn School of Medicine at Mount Sinai, New York, New York, USA

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