Genetic loci associated with heart rate variability and their effects on cardiac disease risk.

Journal: Nature communications

Volume: 8

Issue: 

Year of Publication: 2018

Affiliated Institutions:  Department of Epidemiology, University of Groningen, University Medical Center Groningen, PO Box , Groningen RB, The Netherlands. Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Heidelberglaan , Utrecht CX, The Netherlands. Department of Psychiatry, EMGO Institute for Health and Care Research and Neuroscience Campus Amsterdam, VU University Medical Center/GGZ inGeest, Amsterdam BT, The Netherlands. Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala , Sweden. Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina , USA. Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington , USA. Department of Child and Adolescent Psychiatry/Psychology, Department of Child and Adolescent Psychiatry, PO Box , Rotterdam CB, The Netherlands. Department of Biological Psychology, Behavioral and Movement Sciences, VU University, Amsterdam BT, The Netherlands. Department of Biostatistics, School of Public Health, University of Washington, Seattle, Washington , USA. Montreal Heart Institute, Montreal, Quebec, Canada HT C. Department of Clinical Chemistry, Fimlab Laboratories, Tampere , Finland. Center for Life Course Health Research, University of Oulu, Oulu , Finland. Framingham Heart Study, Framingham, Massachusetts , USA. Department of Clinical Physiology, Sultan Qaboos University Hospital, Muscat-Al Khoudh , Sultanate of Oman. Institute of Medical Epidemiology, Biostatistics and Informatics, Martin-Luther-University Halle-Wittenberg, Halle (Saale) , Germany. Department of Epidemiology, Erasmus MC, University Medical Center Rotterdam, PO Box , Rotterdam CB, The Netherlands. Laboratory of Experimental Cardiology, Department of Heart and Lung, University Medical Center Utrecht, Heidelberglaan , Utrecht CX, The Netherlands. Department of Psychiatry, University of California, San Diego, San Diego, California , USA. Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg , Germany. Department of Health Sciences, University of Milano, Milano , Italy. Department of Psychology, The Ohio State University, Neil Avenue, Columbus, Ohio , USA. Department of Cardiology, University of Groningen, University Medical Center Groningen, PO Box , Groningen RB, The Netherlands. MRC Unit for Lifelong Health and Ageing, University College London, Bedford Place, London WCB JU, UK. Institute of Psychiatry, Psychology &Neuroscience, King's College London, De Crespigny Park, London SE AF, UK. Department of Public Health, Academic Medical Center (AMC), University of Amsterdam, Amsterdam AZ, The Netherlands. Department of Physiology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat Al-Khoudh , Sultanate of Oman. Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts , USA. Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, Georgia , USA. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland , USA. Department of Medical Sciences, Molecular Medicine, Uppsala University, Uppsala , Sweden. Center for Stress and Mental Health (CESAMH), VA San Diego Healthcare System, San Diego, California , USA. Department of Genetics, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht CX, The Netherlands. College of Medicine, Mohammed Bin Rashid University, PO Box , Dubai Healthcare City, United Arab Emirates. Department of Epidemiology and Public Health, University College London, London WCE BT, UK. Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts , USA. Department of Child- and Adolescent Psychiatry, University of Groningen, University Medical Center Groningen, PO Box , Groningen RB, The Netherlands. Center for Complex Disease Genomics, McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland , USA. Program in Medical and Population Genetics, The Broad Institute of Harvard and MIT, Cambridge, Massachusetts , USA. Department of Cardiology, Heart Hospital, Tampere University Hospital, Tampere , Finland. University Health Network and Mount Sinai Hospital Division of Cardiology, Department of Medicine, University of Toronto, Ontario, Canada MS. Department of Molecular and Clinical Medicine, Institute of Medicine, Sahlgrenska University Hospital, University of Gothenburg, Gothenburg, Sweden. Department of Public Health and Caring Sciences, Molecular Geriatrics, Uppsala University, Uppsala , Sweden. Interdisciplinary Center Psychopathology and Emotion regulation, Department of Psychiatry, University of Groningen, University Medical Center Groningen, PO Box , Groningen RB, The Netherlands. Research Unit of Internal Medicine, Medical Research Center Oulu, Oulu University Hospital and University of Oulu, Oulu , Finland. Department of Pediatrics, Tampere University Hospital, Tampere , Finland. INSERM U, Paris Descartes University, Paris , France. Department of Medicine, University of Turku, Turku , Finland. Department of Medical Informatics, Erasmus Medical Center, Rotterdam CE, The Netherlands. Studies Coordinating Centre, Research Unit Hypertension and Cardiovascular Epidemiology, KU Leuven Department of Cardiovascular Sciences, University of Leuven, Leuven , Belgium. Department of Internal Medicine, Division of Vascular Medicine, University of Groningen, University Medical Center Groningen, PO Box , Groningen RB, The Netherlands. Division of Genetic Epidemiology, Institute for Medical Biometry and Statistics, Medical Center-University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg , Germany. Department of Genetics, University of North Carolina, Chapel Hill, North Carolina , USA. Division of Epidemiology, Department of Public Health Sciences, Penn State University College of Medicine, Hershey, Pennsylvania , USA. Division of Cardiovascular Medicine, University of Florida College of Medicine, Gainesville, Florida , USA. Institute for Translational Genomics and Population Sciences, Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California , USA. Li Ka Shing Centre for Health Information and Discovery, The Big Data Institute, University of Oxford, Oxford OX BN, UK. Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford OX BN, UK. Biopharmacy, Department Pharmaceutical Sciences, University of Basel, Basel CH-, Switzerland. Laboratory of Neurogenetics, National Institute on Aging, National Institutes of Health, Bethesda, Maryland , USA. Department of Internal Medicine, Division of Nephrology, University of Groningen, University Medical Center Groningen, PO Box , Groningen RB, The Netherlands. Department of Medicine, University of California, San Diego, San Diego, California , USA. Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg , Germany. DZHK (German Centre for Cardiovascular Research), Partner site Munich Heart Alliance, Munich , Germany. Department of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku , Finland. Department of Medicine, University Hospital Munich, Ludwig-Maximilians-University, Munich , Germany. The New York Academy of Medicine, New York, New York , USA. Group Health Research Institute, Group Health Cooperative, Seattle, Washington , USA. Epidemiological Cardiology Research Center (EPICARE), Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, North Carolina , USA. Cardiovascular Health Research Unit, Division of Cardiology, Departments of Medicine and Epidemiology, University of Washington, Seattle, Washington , USA. Heart Rate Variability Lab, Washington University School of Medicine, St Louis, Missouri , USA. First Department of Cardiology, Interventional Electrocardiology and Hypertension, Jagiellonian University Medical College, Cracow -, Poland. Department of Medical Sciences, Cardiovascular Epidemiology, Uppsala University, Uppsala , Sweden. Department of Cardiology, Leiden University Medical Center, Leiden RC, The Netherlands. Institute for Translational Genomics and Population Sciences, Departments of Pediatrics and Medicine, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, California , USA. Institute for Community Medicine, University Medicine Greifswald, Greifswald , Germany. Public Health Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington , USA. Institute of Innovative Health Technologies-IGHT Jena Ernst-Abbe-Hochschule Jena, Jena , Germany. Departments of Genetics and Neurology University of North Carolina, Chapel Hill, North Carolina , USA. Laboratory of Epidemiology and Population Sciences, National Institute on Aging, National Institutes of Health, Baltimore, Maryland , USA. Institute of Biomedical Technologies, CNR-Italian National Research Council, Milan , Italy. German Cancer Research Centre, Division of Cancer Epidemiology, Heidelberg , Germany. Department of Clinical Physiology, Tampere University Hospital, Tampere , Finland. Department of Physiology, Institute for Cardiovascular Research, VU University Medical Center, De Boelelaan , Amsterdam HV, The Netherlands.

Abstract summary 

Reduced cardiac vagal control reflected in low heart rate variability (HRV) is associated with greater risks for cardiac morbidity and mortality. In two-stage meta-analyses of genome-wide association studies for three HRV traits in up to 53,174 individuals of European ancestry, we detect 17 genome-wide significant SNPs in eight loci. HRV SNPs tag non-synonymous SNPs (in NDUFA11 and KIAA1755), expression quantitative trait loci (eQTLs) (influencing GNG11, RGS6 and NEO1), or are located in genes preferentially expressed in the sinoatrial node (GNG11, RGS6 and HCN4). Genetic risk scores account for 0.9 to 2.6% of the HRV variance. Significant genetic correlation is found for HRV with heart rate (-0.74Authors & Co-authors:  Nolte Ilja M IM Munoz M Loretto ML Tragante Vinicius V Amare Azmeraw T AT Jansen Rick R Vaez Ahmad A von der Heyde Benedikt B Avery Christy L CL Bis Joshua C JC Dierckx Bram B van Dongen Jenny J Gogarten Stephanie M SM Goyette Philippe P Hernesniemi Jussi J Huikari Ville V Hwang Shih-Jen SJ Jaju Deepali D Kerr Kathleen F KF Kluttig Alexander A Krijthe Bouwe P BP Kumar Jitender J van der Laan Sander W SW Lyytikäinen Leo-Pekka LP Maihofer Adam X AX Minassian Arpi A van der Most Peter J PJ Müller-Nurasyid Martina M Nivard Michel M Salvi Erika E Stewart James D JD Thayer Julian F JF Verweij Niek N Wong Andrew A Zabaneh Delilah D Zafarmand Mohammad H MH Abdellaoui Abdel A Albarwani Sulayma S Albert Christine C Alonso Alvaro A Ashar Foram F Auvinen Juha J Axelsson Tomas T Baker Dewleen G DG de Bakker Paul I W PIW Barcella Matteo M Bayoumi Riad R Bieringa Rob J RJ Boomsma Dorret D Boucher Gabrielle G Britton Annie R AR Christophersen Ingrid I Dietrich Andrea A Ehret George B GB Ellinor Patrick T PT Eskola Markku M Felix Janine F JF Floras John S JS Franco Oscar H OH Friberg Peter P Gademan Maaike G J MGJ Geyer Mark A MA Giedraitis Vilmantas V Hartman Catharina A CA Hemerich Daiane D Hofman Albert A Hottenga Jouke-Jan JJ Huikuri Heikki H Hutri-Kähönen Nina N Jouven Xavier X Junttila Juhani J Juonala Markus M Kiviniemi Antti M AM Kors Jan A JA Kumari Meena M Kuznetsova Tatiana T Laurie Cathy C CC Lefrandt Joop D JD Li Yong Y Li Yun Y Liao Duanping D Limacher Marian C MC Lin Henry J HJ Lindgren Cecilia M CM Lubitz Steven A SA Mahajan Anubha A McKnight Barbara B Zu Schwabedissen Henriette Meyer HM Milaneschi Yuri Y Mononen Nina N Morris Andrew P AP Nalls Mike A MA Navis Gerjan G Neijts Melanie M Nikus Kjell K North Kari E KE O'Connor Daniel T DT Ormel Johan J Perz Siegfried S Peters Annette A Psaty Bruce M BM Raitakari Olli T OT Risbrough Victoria B VB Sinner Moritz F MF Siscovick David D Smit Johannes H JH Smith Nicholas L NL Soliman Elsayed Z EZ Sotoodehnia Nona N Staessen Jan A JA Stein Phyllis K PK Stilp Adrienne M AM Stolarz-Skrzypek Katarzyna K Strauch Konstantin K Sundström Johan J Swenne Cees A CA Syvänen Ann-Christine AC Tardif Jean-Claude JC Taylor Kent D KD Teumer Alexander A Thornton Timothy A TA Tinker Lesley E LE Uitterlinden André G AG van Setten Jessica J Voss Andreas A Waldenberger Melanie M Wilhelmsen Kirk C KC Willemsen Gonneke G Wong Quenna Q Zhang Zhu-Ming ZM Zonderman Alan B AB Cusi Daniele D Evans Michele K MK Greiser Halina K HK van der Harst Pim P Hassan Mohammad M Ingelsson Erik E Järvelin Marjo-Riitta MR Kääb Stefan S Kähönen Mika M Kivimaki Mika M Kooperberg Charles C Kuh Diana D Lehtimäki Terho T Lind Lars L Nievergelt Caroline M CM O'Donnell Chris J CJ Oldehinkel Albertine J AJ Penninx Brenda B Reiner Alexander P AP Riese Harriëtte H van Roon Arie M AM Rioux John D JD Rotter Jerome I JI Sofer Tamar T Stricker Bruno H BH Tiemeier Henning H Vrijkotte Tanja G M TGM Asselbergs Folkert W FW Brundel Bianca J J M BJJM Heckbert Susan R SR Whitsel Eric A EA den Hoed Marcel M Snieder Harold H de Geus Eco J C EJC

Study Outcome 

Source Link: Visit source

Statistics
Citations :  Berntson G. G., Cacioppo J. T. & Quigley K. S. Respiratory sinus arrhythmia: autonomic origins, physiological mechanisms, and psychophysiological implications. Psychophysiology 30, 183–196 (1993).
Authors :  164
Identifiers
Doi : 15805
SSN : 2041-1723
Study Population
Male,Female
Mesh Terms
Blood Pressure
Other Terms
Study Design
Case Control Trial,Cross Sectional Study
Study Approach
Quantitative
Country of Study
Publication Country
England