Nature Communications (Aug 2023)
Genetic insights into resting heart rate and its role in cardiovascular disease
- Yordi J. van de Vegte,
- Ruben N. Eppinga,
- M. Yldau van der Ende,
- Yanick P. Hagemeijer,
- Yuvaraj Mahendran,
- Elias Salfati,
- Albert V. Smith,
- Vanessa Y. Tan,
- Dan E. Arking,
- Ioanna Ntalla,
- Emil V. Appel,
- Claudia Schurmann,
- Jennifer A. Brody,
- Rico Rueedi,
- Ozren Polasek,
- Gardar Sveinbjornsson,
- Cecile Lecoeur,
- Claes Ladenvall,
- Jing Hua Zhao,
- Aaron Isaacs,
- Lihua Wang,
- Jian’an Luan,
- Shih-Jen Hwang,
- Nina Mononen,
- Kirsi Auro,
- Anne U. Jackson,
- Lawrence F. Bielak,
- Linyao Zeng,
- Nabi Shah,
- Maria Nethander,
- Archie Campbell,
- Tuomo Rankinen,
- Sonali Pechlivanis,
- Lu Qi,
- Wei Zhao,
- Federica Rizzi,
- Toshiko Tanaka,
- Antonietta Robino,
- Massimiliano Cocca,
- Leslie Lange,
- Martina Müller-Nurasyid,
- Carolina Roselli,
- Weihua Zhang,
- Marcus E. Kleber,
- Xiuqing Guo,
- Henry J. Lin,
- Francesca Pavani,
- Tessel E. Galesloot,
- Raymond Noordam,
- Yuri Milaneschi,
- Katharina E. Schraut,
- Marcel den Hoed,
- Frauke Degenhardt,
- Stella Trompet,
- Marten E. van den Berg,
- Giorgio Pistis,
- Yih-Chung Tham,
- Stefan Weiss,
- Xueling S. Sim,
- Hengtong L. Li,
- Peter J. van der Most,
- Ilja M. Nolte,
- Leo-Pekka Lyytikäinen,
- M. Abdullah Said,
- Daniel R. Witte,
- Carlos Iribarren,
- Lenore Launer,
- Susan M. Ring,
- Paul S. de Vries,
- Peter Sever,
- Allan Linneberg,
- Erwin P. Bottinger,
- Sandosh Padmanabhan,
- Bruce M. Psaty,
- Nona Sotoodehnia,
- Ivana Kolcic,
- The DCCT/EDIC Research Group,
- David O. Arnar,
- Daniel F. Gudbjartsson,
- Hilma Holm,
- Beverley Balkau,
- Claudia T. Silva,
- Christopher H. Newton-Cheh,
- Kjell Nikus,
- Perttu Salo,
- Karen L. Mohlke,
- Patricia A. Peyser,
- Heribert Schunkert,
- Mattias Lorentzon,
- Jari Lahti,
- Dabeeru C. Rao,
- Marilyn C. Cornelis,
- Jessica D. Faul,
- Jennifer A. Smith,
- Katarzyna Stolarz-Skrzypek,
- Stefania Bandinelli,
- Maria Pina Concas,
- Gianfranco Sinagra,
- Thomas Meitinger,
- Melanie Waldenberger,
- Moritz F. Sinner,
- Konstantin Strauch,
- Graciela E. Delgado,
- Kent D. Taylor,
- Jie Yao,
- Luisa Foco,
- Olle Melander,
- Jacqueline de Graaf,
- Renée de Mutsert,
- Eco J. C. de Geus,
- Åsa Johansson,
- Peter K. Joshi,
- Lars Lind,
- Andre Franke,
- Peter W. Macfarlane,
- Kirill V. Tarasov,
- Nicholas Tan,
- Stephan B. Felix,
- E-Shyong Tai,
- Debra Q. Quek,
- Harold Snieder,
- Johan Ormel,
- Martin Ingelsson,
- Cecilia Lindgren,
- Andrew P. Morris,
- Olli T. Raitakari,
- Torben Hansen,
- Themistocles Assimes,
- Vilmundur Gudnason,
- Nicholas J. Timpson,
- Alanna C. Morrison,
- Patricia B. Munroe,
- David P. Strachan,
- Niels Grarup,
- Ruth J. F. Loos,
- Susan R. Heckbert,
- Peter Vollenweider,
- Caroline Hayward,
- Kari Stefansson,
- Philippe Froguel,
- Leif Groop,
- Nicholas J. Wareham,
- Cornelia M. van Duijn,
- Mary F. Feitosa,
- Christopher J. O’Donnell,
- Mika Kähönen,
- Markus Perola,
- Michael Boehnke,
- Sharon L. R. Kardia,
- Jeanette Erdmann,
- Colin N. A. Palmer,
- Claes Ohlsson,
- David J. Porteous,
- Johan G. Eriksson,
- Claude Bouchard,
- Susanne Moebus,
- Peter Kraft,
- David R. Weir,
- Daniele Cusi,
- Luigi Ferrucci,
- Sheila Ulivi,
- Giorgia Girotto,
- Adolfo Correa,
- Stefan Kääb,
- Annette Peters,
- John C. Chambers,
- Jaspal S. Kooner,
- Winfried März,
- Jerome I. Rotter,
- Andrew A. Hicks,
- J. Gustav Smith,
- Lambertus A. L. M. Kiemeney,
- Dennis O. Mook-Kanamori,
- Brenda W. J. H. Penninx,
- Ulf Gyllensten,
- James F. Wilson,
- Stephen Burgess,
- Johan Sundström,
- Wolfgang Lieb,
- J. Wouter Jukema,
- Mark Eijgelsheim,
- Edward L. M. Lakatta,
- Ching-Yu Cheng,
- Marcus Dörr,
- Tien-Yin Wong,
- Charumathi Sabanayagam,
- Albertine J. Oldehinkel,
- Harriette Riese,
- Terho Lehtimäki,
- Niek Verweij,
- Pim van der Harst
Affiliations
- Yordi J. van de Vegte
- Department of Cardiology, University of Groningen, University Medical Center Groningen
- Ruben N. Eppinga
- Department of Cardiology, Isala Zwolle ziekenhuis
- M. Yldau van der Ende
- Department of Cardiology, University medical Center Utrecht
- Yanick P. Hagemeijer
- Department of Cardiology, University of Groningen, University Medical Center Groningen
- Yuvaraj Mahendran
- The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medicine Science, University of Copenhagen
- Elias Salfati
- Department of Medicine, Stanford University School of Medicine
- Albert V. Smith
- Department of Biostatistics, University of Michigan
- Vanessa Y. Tan
- Bristol Medical School, Population Health Sciences, University of Bristol
- Dan E. Arking
- McKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine
- Ioanna Ntalla
- Clinical Pharmacology and Precision Medicine, William Harvey Research Institute, Barts and The London Faculty of Medicine and Dentistry, Queen Mary University of London
- Emil V. Appel
- The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medicine Science, University of Copenhagen
- Claudia Schurmann
- The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai
- Jennifer A. Brody
- Medicine, University of Washington
- Rico Rueedi
- Department of Computational Biology, University of Lausanne
- Ozren Polasek
- Department of Public Health, University of Split School of Medicine
- Gardar Sveinbjornsson
- deCODE genetics / Amgen Inc.
- Cecile Lecoeur
- UMR 8199, University of Lille Nord de France
- Claes Ladenvall
- Clinial Genomics Uppsala, Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University
- Jing Hua Zhao
- BHF Cardiovascular Epidemiology Unit, Department of Public Health and Primary Care, Victor Phillip Dahdaleh Heart & Lung Research Institute, University of Cambridge
- Aaron Isaacs
- CARIM School for Cardiovascular Diseases, Maastricht Centre for Systems Biology (MaCSBio), Department of Physiology, Maastricht University
- Lihua Wang
- Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine
- Jian’an Luan
- MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine
- Shih-Jen Hwang
- Division of Intramural Research, National Heart Lung and Blood Institute, NIH, USA
- Nina Mononen
- Department of Clinical Chemistry, Fimlab Laboratories
- Kirsi Auro
- Department of Health, unit of genetics and biomarkers, , National Institute for Health and Welfare, Finland
- Anne U. Jackson
- Department of Biostatistics and Center for Statistical Genetics, University of Michigan
- Lawrence F. Bielak
- Department of Epidemiology, University of Michigan
- Linyao Zeng
- Department of Cardiology, Deutsches Herzzentrum München, Technische Universität München
- Nabi Shah
- Division of Population Health and Genomics, School of Medicine, University of Dundee
- Maria Nethander
- Sahlgrenska Osteoporosis Centre, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg
- Archie Campbell
- Centre for Genomic and Experimental Medicine, Institute of Genetics & Cancer, University of Edinburgh
- Tuomo Rankinen
- Human Genomics Laboratory, Pennington Biomedical Research Center
- Sonali Pechlivanis
- Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, University Duisburg-Essen
- Lu Qi
- Department of Epidemiology, Tulane University
- Wei Zhao
- Department of Epidemiology, University of Michigan
- Federica Rizzi
- Unit of Biomedicine, Bio4Dreams-Business Nursery for Life Sciences
- Toshiko Tanaka
- Longitudinal Study Section, National Institute on Aging
- Antonietta Robino
- Institute for Maternal and Child Health - IRCCS “Burlo Garofolo”
- Massimiliano Cocca
- Institute for Maternal and Child Health - IRCCS “Burlo Garofolo”
- Leslie Lange
- Medicine, University of Colorado Anschutz Medical Campus
- Martina Müller-Nurasyid
- IBE, Ludwig-Maximilians-University Munich, LMU Munich
- Carolina Roselli
- Institute of Genetic Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health
- Weihua Zhang
- Department of Epidemiology and Biostatistics, Imperial College London
- Marcus E. Kleber
- Vth Department of Medicine (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg
- Xiuqing Guo
- Pediatrics, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA
- Henry J. Lin
- Pediatrics, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA
- Francesca Pavani
- Institute for Biomedicine, Eurac Research
- Tessel E. Galesloot
- Radboud university medical center
- Raymond Noordam
- Department of Internal Medicine, section Gerontology and Geriatrics, Leiden University Medical Center
- Yuri Milaneschi
- Department of Psychiatry, Amsterdam Public Health, Amsterdam UMC, Amsterdam UMC, Vrije Universiteit, Amsterdam
- Katharina E. Schraut
- Centre for Cardiovascular Science, Queen’s Medical Research Institute, University of Edinburgh
- Marcel den Hoed
- The Beijer laboratory and Department of Immunology, Genetics and Pathology, Uppsala University and Science for Life Laboratory
- Frauke Degenhardt
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel
- Stella Trompet
- Department of Internal Medicine, section Gerontology and Geriatrics, Leiden University Medical Center
- Marten E. van den Berg
- Department of Epidemiology, Erasmus Medical Center
- Giorgio Pistis
- Institute of Genetics and Biomedic Research (IRGB), Italian National Research Council (CNR)
- Yih-Chung Tham
- Singapore Eye Research Institute, Singapore National Eye Centre
- Stefan Weiss
- Interfaculty Institute for Genetics and Functional Genomics, University Medicine Greifswald
- Xueling S. Sim
- Saw Swee Hock School of Public Health, National University Health System and National University of Singapore
- Hengtong L. Li
- Singapore Eye Research Institute, Singapore National Eye Centre
- Peter J. van der Most
- Department of Epidemiology, University of Groningen, University Medical Center Groningen
- Ilja M. Nolte
- Department of Epidemiology, University of Groningen, University Medical Center Groningen
- Leo-Pekka Lyytikäinen
- Department of Clinical Chemistry, Fimlab Laboratories
- M. Abdullah Said
- Department of Cardiology, University of Groningen, University Medical Center Groningen
- Daniel R. Witte
- Department of Public Health, Aarhus University
- Carlos Iribarren
- Division of Research, Kaiser Permenente of Northern California
- Lenore Launer
- National Institute on Aging
- Susan M. Ring
- Bristol Medical School, Population Health Sciences, University of Bristol
- Paul S. de Vries
- Department of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas Health Science Center at Houston, School of Public Health
- Peter Sever
- National Heart and Lung Institute, Imperial College London
- Allan Linneberg
- Center for Clinical Research and Prevention, Bispebjerg and Frederiksberg Hospital
- Erwin P. Bottinger
- The Charles Bronfman Institute for Personalized Medicine, The Icahn School of Medicine at Mount Sinai
- Sandosh Padmanabhan
- Institute of Cardiovascular and Medical Sciences, University of Glasgow
- Bruce M. Psaty
- Departments of Medicine, Epidemiology and Health Systems and Population Health, University of Washington
- Nona Sotoodehnia
- Medicine and Epidemiology, University of Washington
- Ivana Kolcic
- Department of Public Health, University of Split School of Medicine
- The DCCT/EDIC Research Group
- David O. Arnar
- deCODE genetics / Amgen Inc.
- Daniel F. Gudbjartsson
- deCODE genetics / Amgen Inc.
- Hilma Holm
- deCODE genetics / Amgen Inc.
- Beverley Balkau
- Centre for Research in Epidemiology and Population Health, Institut national de la santé et de la recherche médicale
- Claudia T. Silva
- Genetic Epidemiology Unit, Dept. of Epidemiology, Erasmus University Medical Center
- Christopher H. Newton-Cheh
- Cardiology Section, Massachusetts general hospital,
- Kjell Nikus
- Department of Cardiology, Heart Center, Tampere University Hospital
- Perttu Salo
- Department of Health, unit of genetics and biomarkers, , National Institute for Health and Welfare, Finland
- Karen L. Mohlke
- Department of Genetics, University of North Carolina
- Patricia A. Peyser
- Department of Epidemiology, University of Michigan
- Heribert Schunkert
- Department of Cardiology, Deutsches Herzzentrum München, Technische Universität München
- Mattias Lorentzon
- Sahlgrenska Osteoporosis Centre, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg
- Jari Lahti
- Department of Psychology and Logopedics, University of Helsinki
- Dabeeru C. Rao
- Division of Biostatistics, Washington University
- Marilyn C. Cornelis
- Preventive Medicine, Northwestern University
- Jessica D. Faul
- Survey Research Center, Institute for Social Research, University of Michigan
- Jennifer A. Smith
- Department of Epidemiology, University of Michigan
- Katarzyna Stolarz-Skrzypek
- Department of Cardiology, Interventional Electrocardiology and Hypertension, Jagiellonian University Medical College
- Stefania Bandinelli
- Geriatric Unit, Unità sanitaria locale Toscana Centro
- Maria Pina Concas
- Institute for Maternal and Child Health - IRCCS “Burlo Garofolo”
- Gianfranco Sinagra
- Cardiovascular Department, “Ospedali Riuniti and University of Trieste”
- Thomas Meitinger
- Institute of Human Genetics, Klinikum rechts der Isar, Technische Universität München
- Melanie Waldenberger
- Research Unit Molecular Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health
- Moritz F. Sinner
- German Centre for Cardiovascular Research (DZHK), partner site: Munich Heart Alliance
- Konstantin Strauch
- Institute of Medical Biostatistics, Epidemiology and Informatics (IMBEI), University Medical Center, Johannes Gutenberg University
- Graciela E. Delgado
- Vth Department of Medicine (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg
- Kent D. Taylor
- Pediatrics, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA
- Jie Yao
- Pediatrics, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA
- Luisa Foco
- Institute for Biomedicine, Eurac Research
- Olle Melander
- Department of Internal Medicine, Clinical Sciences, Lund University and Skåne University Hospital
- Jacqueline de Graaf
- Radboud university medical center
- Renée de Mutsert
- Department of Clinical Epidemiology, Leiden University Medical Center
- Eco J. C. de Geus
- Biological Psychology, EMGO+ Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University
- Åsa Johansson
- Department of Immunology, Genetics and Pathology, Uppsala University
- Peter K. Joshi
- Centre for Global Health Research, Usher Institute, University of Edinburgh
- Lars Lind
- Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University Hospital
- Andre Franke
- Institute of Clinical Molecular Biology, Christian-Albrechts-University of Kiel
- Peter W. Macfarlane
- Institute of Health and Wellbeing, Faculty of Medicine, University of Glasgow
- Kirill V. Tarasov
- Laboratory of Cardiovascular Sciences, Intramural Research Program, National Institute on Aging, National Institutes of Health
- Nicholas Tan
- Singapore Eye Research Institute, Singapore National Eye Centre
- Stephan B. Felix
- DZHK (German Center for Cardiovascular Research), Partner Site Greifswald
- E-Shyong Tai
- Singapore Eye Research Institute, Singapore National Eye Centre
- Debra Q. Quek
- Singapore Eye Research Institute, Singapore National Eye Centre
- Harold Snieder
- Department of Epidemiology, University of Groningen, University Medical Center Groningen
- Johan Ormel
- Department of Psychiatry, University of Groningen, University Medical Center Groningen
- Martin Ingelsson
- Department of Public Health and Caring Sciences, Molecular Geriatrics, Uppsala University
- Cecilia Lindgren
- Genetic and Genomic Epidemiology Unit, Wellcome Trust Centre for Human Genetics, University of Oxford
- Andrew P. Morris
- Genetic and Genomic Epidemiology Unit, Wellcome Trust Centre for Human Genetics, University of Oxford
- Olli T. Raitakari
- Centre for Population Health Research, University of Turku and Turku University Hospital
- Torben Hansen
- The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medicine Science, University of Copenhagen
- Themistocles Assimes
- Department of Medicine, Stanford University School of Medicine
- Vilmundur Gudnason
- Faculty of Medicine, University of Iceland
- Nicholas J. Timpson
- MRC Integrative Epidemiology Unit, University of Bristol
- Alanna C. Morrison
- Department of Epidemiology, Human Genetics, and Environmental Sciences, University of Texas Health Science Center at Houston, School of Public Health
- Patricia B. Munroe
- Clinical Pharmacology and Precision Medicine, William Harvey Research Institute, Barts and The London Faculty of Medicine and Dentistry, Queen Mary University of London
- David P. Strachan
- Population Health Research Institute, St George’s, University of London
- Niels Grarup
- The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medicine Science, University of Copenhagen
- Ruth J. F. Loos
- The Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medicine Science, University of Copenhagen
- Susan R. Heckbert
- Department of Epidemiology, University of Washington
- Peter Vollenweider
- Department of Medicine, Internal Medicine, Lausanne University hospital
- Caroline Hayward
- MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh
- Kari Stefansson
- deCODE genetics / Amgen Inc.
- Philippe Froguel
- Department of Metabolism, Imperial College London
- Leif Groop
- Lund University Diabetes Center, Department of Clinical Sciences, Lund University
- Nicholas J. Wareham
- MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine
- Cornelia M. van Duijn
- Genetic Epidemiology Unit, Dept. of Epidemiology, Erasmus University Medical Center
- Mary F. Feitosa
- Division of Statistical Genomics, Department of Genetics, Washington University School of Medicine
- Christopher J. O’Donnell
- Cardiology Section, VA Boston Healthcare System, Harvard Medical School
- Mika Kähönen
- Department of Clinical Physiology, Tampere University Hospital
- Markus Perola
- Department of Health, unit of genetics and biomarkers, , National Institute for Health and Welfare, Finland
- Michael Boehnke
- Department of Biostatistics and Center for Statistical Genetics, University of Michigan
- Sharon L. R. Kardia
- Department of Epidemiology, University of Michigan
- Jeanette Erdmann
- Institute for Cardiogenetics, University of Lübeck
- Colin N. A. Palmer
- Division of Population Health and Genomics, School of Medicine, University of Dundee
- Claes Ohlsson
- Sahlgrenska Osteoporosis Centre, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg
- David J. Porteous
- Centre for Genomic and Experimental Medicine, Institute of Genetics & Molecular Medicine, University of Edinburgh
- Johan G. Eriksson
- Department of General practice and primary care, University of Helsinki
- Claude Bouchard
- Human Genomics Laboratory, Pennington Biomedical Research Center
- Susanne Moebus
- Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, University Duisburg-Essen
- Peter Kraft
- Epidemiology, Harvard T.H. Chan School of Public Health
- David R. Weir
- Survey Research Center, Institute for Social Research, University of Michigan
- Daniele Cusi
- Unit of Biomedicine, Bio4Dreams-Business Nursery for Life Sciences
- Luigi Ferrucci
- Longitudinal Study Section, National Institute on Aging
- Sheila Ulivi
- Institute for Maternal and Child Health - IRCCS “Burlo Garofolo”
- Giorgia Girotto
- Institute for Maternal and Child Health - IRCCS “Burlo Garofolo”
- Adolfo Correa
- Jackson Heart Study, University of Mississippi Medical Center
- Stefan Kääb
- German Centre for Cardiovascular Research (DZHK), partner site: Munich Heart Alliance
- Annette Peters
- Institute of Epidemiology, Helmholtz Zentrum München - German Research Center for Environmental Health
- John C. Chambers
- Department of Epidemiology and Biostatistics, Imperial College London
- Jaspal S. Kooner
- Department of Cardiology, Ealing Hospital, London North West University Healthcare NHS Trust
- Winfried März
- Vth Department of Medicine (Nephrology, Hypertensiology, Rheumatology, Endocrinology, Diabetology), Medical Faculty Mannheim, University of Heidelberg
- Jerome I. Rotter
- Pediatrics, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA
- Andrew A. Hicks
- Institute for Biomedicine, Eurac Research
- J. Gustav Smith
- Department of Cardiology, Clinical Sciences, Lund University and Skåne University Hospital
- Lambertus A. L. M. Kiemeney
- Radboud university medical center
- Dennis O. Mook-Kanamori
- Department of Clinical Epidemiology, Leiden University Medical Center
- Brenda W. J. H. Penninx
- Department of Psychiatry, Amsterdam Public Health, Amsterdam UMC, Amsterdam UMC, Vrije Universiteit, Amsterdam
- Ulf Gyllensten
- Department of Immunology, Genetics and Pathology, Uppsala University
- James F. Wilson
- Centre for Global Health Research, Usher Institute, University of Edinburgh
- Stephen Burgess
- MRC Biostatistics Unit, University of Cambridge
- Johan Sundström
- Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University Hospital
- Wolfgang Lieb
- Institute of Epidemiology and Biobank PopGen, Kiel University
- J. Wouter Jukema
- Department of Cardiology, Leiden University Medical Center
- Mark Eijgelsheim
- Department of Epidemiology, Erasmus Medical Center
- Edward L. M. Lakatta
- Laboratory of Cardiovascular Sciences, Intramural Research Program, National Institute on Aging, National Institutes of Health
- Ching-Yu Cheng
- Singapore Eye Research Institute, Singapore National Eye Centre
- Marcus Dörr
- DZHK (German Center for Cardiovascular Research), Partner Site Greifswald
- Tien-Yin Wong
- Singapore Eye Research Institute, Singapore National Eye Centre
- Charumathi Sabanayagam
- Singapore Eye Research Institute, Singapore National Eye Centre
- Albertine J. Oldehinkel
- Interdisciplinary Center Psychopathology and Emotion Regulation, University of Groningen, University Medical Center Groningen
- Harriette Riese
- Department of Psychiatry, University of Groningen, University Medical Center Groningen
- Terho Lehtimäki
- Department of Clinical Chemistry, Fimlab Laboratories
- Niek Verweij
- Department of Cardiology, University of Groningen, University Medical Center Groningen
- Pim van der Harst
- Department of Cardiology, University of Groningen, University Medical Center Groningen
- DOI
- https://doi.org/10.1038/s41467-023-39521-2
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 21
Abstract
Abstract Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.
