Author
Affilliation
Abstract
The 3-dimensional spatial and 2-dimensional frontal QRS-T angles are measures derived from the vectorcardiogram. They are independent risk predictors for arrhythmia, but the underlying biology is unknown. Using multi-ancestry genome-wide association studies we identify 61 (58 previously unreported) loci for the spatial QRS-T angle (N = 118,780) and 11 for the frontal QRS-T angle (N = 159,715). Seven out of the 61 spatial QRS-T angle loci have not been reported for other electrocardiographic measures. Enrichments are observed in pathways related to cardiac and vascular development, muscle contraction, and hypertrophy. Pairwise genome-wide association studies with classical ECG traits identify shared genetic influences with PR interval and QRS duration. Phenome-wide scanning indicate associations with atrial fibrillation, atrioventricular block and arterial embolism and genetically determined QRS-T angle measures are associated with fascicular and bundle branch block (and also atrioventricular block for the frontal QRS-T angle). We identify potential biology involved in the QRS-T angle and their genetic relationships with cardiovascular traits and diseases, may inform future research and risk prediction.
Publisher
Nature Pub. Group
Citation
YOUNG, William J et al. Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease. Nature Communications, v. 14, n. 1, 1411, 2023. doi: 10.1038/s41467-023-36997-w.
ISSN
2041-1723
Notes
Jeffrey Haessler
Public Health Sciences Division. Fred Hutchinson Cancer Center. Seattle, WA, USA.
Jan-Walter Benjamins
University of Groningen. University Medical Center Groningen. Department of Cardiology. Groningen, the Netherlands.
Linda Repetto
Centre for Global Health Research. Usher Institute. University of Edinburgh. Edinburgh, Scotland.
Jie Yao
Institute for Translational Genomics and Population Sciences. Torrance, CA, USA./The Lundquist Institute at Harbor-UCLA Medical Center. Torrance, CA, USA.
Aaron Isaacs
Dept. of Physiology. Cardiovascular Research Institute Maastricht. Maastricht University, Maastricht. the Netherlands/Center for Systems Biology. Maastricht University. Maastricht, the Netherlands.
Andrew R Harper
Radcliffe Department of Medicine. University of Oxford. Division of Cardiovascular Medicine. John Radcliffe Hospital. Oxford, UK/Wellcome Centre for Human Genetics. Roosevelt Drive, Oxford, UK.
Julia Ramirez
William Harvey Research Institute. Clinical Pharmacology. Queen Mary University of London. London, UK /Institute of Cardiovascular Sciences. University of College London. London, UK/Aragon Institute of Engineering Research. University of Zaragoza. Zaragoza, Spain/Center of Biomedical Research Network. Bioengineering, Biomaterials and Nanomedicine. Zaragoza, Spain.
Sophie Garnier
Sorbonne Universite. Research Unit on Cardiovascular Disorders. Metabolism and Nutrition. Team Genomics & Pathophysiology of Cardiovascular Disease. Paris, Franc/ICAN Institute for Cardiometabolism and Nutrition. Paris, France.
Stefan van Duijvenboden
William Harvey Research Institute. Clinical Pharmacology. Queen Mary University of London. London, UK/ Institute of Cardiovascular Sciences. University of College London. London, UK.
Antoine R Baldassari
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Maria Pina Concas
Institute for Maternal and Child Health - IRCCS "Burlo Garofolo". Trieste, Italy.
ThuyVy Duong
McKusick-Nathans Institute. Department of Genetic Medicine. Johns Hopkins University School of Medicine. Baltimore, MD, USA.
Luisa Foco
Eurac Research. Institute for Biomedicine. University of Lübeck. Bolzano, Italy.
Jonas L Isaksen
Laboratory of Experimental Cardiology. Department of Biomedical Sciences. University of Copenhagen. Copenhagen, Denmark.
Hao Mei
Department of Data Science. University of Mississippi Medical Center. Jackson, MS, USA.
Raymond Noordam
Department of Internal Medicine. section of Gerontology and Geriatrics. Leiden University Medical Center. Leiden, the Netherlands.
Casia Nursyifa
Novo Nordisk Foundation Center for Basic Metabolic Research. Faculty of Health and Medical Sciences. University of Copenhagen. Copenhagen, Denmark.
Anne Richmond
MRC Human Genetics Unit. Institute of Genetics and Cancer. University of Edinburgh. Edinburgh, Scotland.
Meddly L Santolalla
Department of Genetics, Ecology and Evolution. Instituto de Ciências Biológicas. Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brazil/Emerge, Emerging Diseases and Climate Change Research Unit. School of Public Health and Administration. Universidad Peruana Cayetano Heredia. Lima, Peru.
Colleen M Sitlani
Cardiovascular Health Research Unit. Department of Medicine. University of Washington. Seattle, WA, USA.
Negin Soroush
Department of Epidemiology. Erasmus Medical Center. Rotterdam, the Netherlands.
Sébastien Thériault
Population Health Research Institute. McMaster University. Hamilton, ON, Canada/Department of Molecular Biology. Medical Biochemistry and Pathology. Université Laval, Quebec. QC, Canada.
Stella Trompet
Department of Internal Medicine. section of Gerontology and Geriatrics. Leiden University Medical Center. Leiden, the Netherlands/Department of Cardiology. Leiden University Medical Center. Leiden, the Netherlands.
Stefanie Aeschbacher
Julius Global Health. University Utrecht Medical Center. Utrecht, the Netherlands.
Fariba Ahmadizar 27 32, Alvaro Alonso
Department of Epidemiology. Rollins School of Public Health. Emory University. Atlanta, GA, USA.
Jennifer A Brody
Cardiovascular Health Research Unit. Department of Medicine. University of Washington. Seattle, WA, USA.
Archie Campbell
Usher Institute. University of Edinburgh. Edinburgh, UK/Health Data Research UK. University of Edinburgh., Edinburgh, UK/Centre for Genomic and Experimental Medicine. Institute of Genéticos and Cancer. University of Edinburgh. Western General Hospital. Edinburgh, UK.
Adolfo Correa
Departments of Medicine. Pediatrics and Population Health Science. University of Mississippi Medical Center. Jackson, MS, USA.
Dawood Darbar
Department of Medicine. University of Illinois at Chicago. Chicago, IL, USA.
Antonio De Luca
Cardiothoracovascular Department. Division of Cardiology. Azienda Sanitaria Universitaria Giuliano Isontina and University of Trieste. Trieste, Italy.
Jean-François Deleuze
Université Paris-Saclay. Centre National de Recherche en Génomique Humaine. Evry, France/Laboratory of Excellence GENMED. Paris, France/Centre d'Etude du Polymorphisme Humain. Fondation Jean Dausset. Paris, France.
Christina Ellervik
Department of Data and Data Support, Region Zealand, 4180, Sorø, Denmark/Department of Clinical Medicine. Faculty of Health and Medical Sciences. University of Copenhagen. Copenhagen, Denmark/Department of Laboratory Medicine. Boston Children's Hospital. Harvard Medical School. Boston, MA, USA.
Christian Fuchsberger
Eurac Research. Institute for Biomedicine. University of Lübeck. Bolzano, Italy/Department of Biostatistics. University of Michigan School of Public Health, Ann Arbor, MI, USA/ Center for Statistical Genetics, University of Michigan School of Public Health. Ann Arbor, MI, USA.
Anuj Goel
Radcliffe Department of Medicine. University of Oxford. Division of Cardiovascular Medicine. John Radcliffe Hospital. Oxford, UK/Wellcome Centre for Human Genetics. Roosevelt Drive, Oxford, UK.
Christopher Grace
Radcliffe Department of Medicine. University of Oxford. Division of Cardiovascular Medicine. John Radcliffe Hospital. Oxford, UK/Wellcome Centre for Human Genetics. Roosevelt Drive, Oxford, UK.
Xiuqing Guo
Institute for Translational Genomics and Population Sciences. Torrance, CA, USA./The Lundquist Institute at Harbor-UCLA Medical Center. Torrance, CA, USA/Department of Pediatrics. Harbor-UCLA Medical Center. Torrance, CA, USA/Department of Pediatrics. David Geffen School of Medicine at UCLA. Los Angeles, CA, USA.
Torben Hansen
Novo Nordisk Foundation Center for Basic Metabolic Research. Faculty of Health and Medical Sciences. University of Copenhagen. Copenhagen, Denmark.
Susan R Heckbert
Cardiovascular Health Research Unit. Department of Medicine. University of Washington. Seattle, WA, USA/Department of Epidemiology. University of Washington. Seattle, WA, USA.
Rebecca D Jackson
Center for Clinical and Translational Science. Ohio State Medical Center. Columbus, OH, USA.
Jan A Kors
Department of Medical Informatics. Erasmus University Medical Center. Rotterdam, the Netherlands.
Allan Linneberg
Center for Clinical Research and Prevention. Bispebjerg and Frederiksberg Hospital. København, Denmark/Department of Clinical Medicine. Faculty of Health and Medical Sciences. University of Copenhagen. Copenhagen, Denmark.
Peter W Macfarlane
Institute of Health and Wellbeing. School of Health and Wellbeing. College of Medical, Veterinary and Life Sciences. University of Glasgow, Glasgow, UK.
Alanna C Morrison
Human Genetics Center. Department of Epidemiology, Human Genetics, and Environmental Sciences. School of Public Health. The University of Texas Health Science Center at Houston. Houston, TX, USA.
Pau Navarro
MRC Human Genetics Unit. Institute of Genetics and Cancer. University of Edinburgh. Edinburgh, Scotland
David J Porteous
Centre for Genomic and Experimental Medicine. Institute of Genetics and Cancer. University of Edinburgh. Western General Hospital. Edinburgh, UK/Centre for Cognitive Ageing and Cognitive Epidemiology. University of Edinburgh. Edinburgh, UK.
Peter P Pramstaller
Eurac Research. Institute for Biomedicine. University of Lübeck. Bolzano, Italy/Department of Neurology. University of Lübeck. Lübeck, Germany.
Alexander P Reiner
Department of Epidemiology. University of Washington. Seattle, WA, USA/ Fred Hutchinson Cancer Center. University of Washington. Seattle, WA, USA.
Lorenz Risch
Labormedizinisches zentrum Dr. Risch. Vaduz, Liechtenstein/Faculty of Medical Sciences. Private University in the Principality of Liechtenstein. Triesen, Liechtenstein/Center of Laboratory Medicine. University Institute of Clinical Chemistry. University of Bern, Inselspital. Bern, Switzerland.
Ulrich Schotten
Dept. of Physiology. Cardiovascular Research Institute Maastricht. Maastricht University, Maastricht. the Netherlands.
Xia Shen
Centre for Global Health Research. Usher Institute. University of Edinburgh. Edinburgh, Scotland/Department of Medical Epidemiology and Biostatistics. Karolinska Institutet. Stockholm, Sweden/Greater Bay Area Institute of Precision Medicine. Fudan University. Nansha District, Guangzhou, China.
Gianfranco Sinagra
Cardiothoracovascular Department. Division of Cardiology. Azienda Sanitaria Universitaria Giuliano Isontina and University of Trieste. Trieste, Italy.
Elsayed Z Soliman
Epidemiological Cardiology Research Center. Wake Forest School of Medicine. Winston Salem, NC, USA.
Monika Stoll
Maastricht Center for Systems Biology. Maastricht University. Maastricht, the Netherlands/Dept. of Biochemistry. Cardiovascular Research Institute Maastricht. Maastricht University. Maastricht, the Netherlands/Institute of Human Genetics, Genetic Epidemiology, University of Muenster, Muenster, Germany.
Eduardo Tarazona-Santos
Department of Genetics, Ecology and Evolution. Instituto de Ciências Biológicas. Universidade Federal de Minas Gerais. Belo Horizonte, MG, Brazil.
Andrew Tinker
William Harvey Research Institute. Clinical Pharmacology. Queen Mary University of London. London, UK/NIHR Barts Cardiovascular Biomedical Research Centre. Barts and The London School of Medicine and Dentistry. Queen Mary University of London. London, UK.
Katerina Trajanoska
Department of Internal Medicine. Erasmus Medical Center. Rotterdam, the Netherlands.
Eric Villard
Sorbonne Universite. Research Unit on Cardiovascular Disorders. Metabolism and Nutrition. Team Genomics & Pathophysiology of Cardiovascular Disease. Paris, France/ICAN Institute for Cardiometabolism and Nutrition. Paris, France.
Helen R Warren
William Harvey Research Institute. Clinical Pharmacology. Queen Mary University of London. London, UK/NIHR Barts Cardiovascular Biomedical Research Centre. Barts and The London School of Medicine and Dentistry. Queen Mary University of London. London, UK.
Eric A Whitsel
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA/ Department of Medicine. School of Medicine. University of North Carolina. Chapel Hill, NC, USA.
Kerri L Wiggins
Cardiovascular Health Research Unit. Department of Medicine. University of Washington. Seattle, WA, USA.
Dan E Arking
McKusick-Nathans Institute. Department of Genetic Medicine. Johns Hopkins University School of Medicine. Baltimore, MD, USA.
Christy L Avery
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
David Conen
Population Health Research Institute. McMaster University. Hamilton, ON, Canada.
Giorgia Girotto
Institute for Maternal and Child Health - IRCCS "Burlo Garofolo". Trieste, Italy/ Department of Medical. Surgery and Health Sciences. University of Trieste. Trieste, Italy.
Niels Grarup
Novo Nordisk Foundation Center for Basic Metabolic Research. Faculty of Health and Medical Sciences. University of Copenhagen. Copenhagen, Denmark.
Caroline Hayward
MRC Human Genetics Unit. Institute of Genetics and Cancer. University of Edinburgh. Western General Hospital. Edinburgh, UK.
J Wouter Jukema
Department of Cardiology. Leiden University Medical Center. Leiden, the Netherlands/ Netherlands Heart Institute. Utrecht, the Netherlands/Durrer Center for Cardiovascular Research. Amsterdam, the Netherlands.
Dennis O Mook-Kanamori
Department of Clinical Epidemiology. Leiden University Medical Center. Leiden, the Netherlands/ Department of Public Health and Primary Care. Leiden University Medical Center. Leiden, the Netherlands
Morten Salling Olesen
Department of Biomedical Sciences. University of Copenhagen. Copenhagen, Denmark.
Sandosh Padmanabhan
Institute of Cardiovascular and Medical Sciences. University of Glasgow. Glasgow, UK.
Bruce M Psaty
Cardiovascular Health Research Unit. Department of Medicine. University of Washington. Seattle, WA, USA/ Department of Epidemiology. University of Washington. Seattle, WA, USA/ Department of Health Systems and Population Health. University of Washington. Seattte, WA, USA.
Cristian Pattaro
Eurac Research. Institute for Biomedicine. University of Lübeck. Bolzano, Italy.
Antonio Luiz P Ribeiro 81 82, Jerome I Rotter 6 48 83, Bruno H Stricker
Department of Epidemiology. Erasmus Medical Center. Rotterdam, the Netherlands.
Pim van der Harst
University of Groningen. University Medical Center Groningen. Department of Cardiology. Groningen, the Netherlands/Department of Cardiology. Heart and Lung Division. University Medical Center Utrecht. Utrecht, the Netherlands.
Cornelia M van Duijn
Nuffield Department of Population Health. University of Oxford. Oxford, UK/Department of Epidemiology. Erasmus MC University Medical Center. Rotterdam, the Netherlands.
Niek Verweij
University of Groningen. University Medical Center Groningen. Department of Cardiology. Groningen, the Netherlands
James G Wilson
Department of Physiology and Biophysics. University of Mississippi Medical Center.Jackson, MS, USA/Department of Cardiology. Beth Israel Deaconess Medical Center. Boston, MA, USA.
Michele Orini
Barts Heart Centre. St Bartholomew's Hospital. Barts Health NHS trust. London, UK/ Institute of Cardiovascular Sciences. University of College London. London, UK.
Philippe Charron
Sorbonne Universite. Research Unit on Cardiovascular Disorders. Metabolism and Nutrition. Team Genomics & Pathophysiology of Cardiovascular Disease. Paris, France/ICAN Institute for Cardiometabolism and Nutrition. Paris, France/ APHP. Cardiology Department. Pitié-Salpêtrière Hospital. Paris, France/APHP. Département de Génétique. Centre de Référence Maladies Cardiaques Héréditaires. Pitié-Salpêtrière Hospital. Paris, France.
Hugh Watkins
Radcliffe Department of Medicine. University of Oxford. Division of Cardiovascular Medicine. John Radcliffe Hospital. Oxford, UK/ Wellcome Centre for Human Genetics. Roosevelt Drive, Oxford, UK.
Charles Kooperberg
Public Health Sciences Division. Fred Hutchinson Cancer Center. Seattle, WA, USA.
Henry J Lin
Institute for Translational Genomics and Population Sciences. Torrance, CA, USA./The Lundquist Institute at Harbor-UCLA Medical Center. Torrance, CA, USA/ Department of Pediatrics. Harbor-UCLA Medical Center. Torrance, CA, USA/ Department of Pediatrics. David Geffen School of Medicine at UCLA. Los Angeles, CA, USA.
James F Wilson
Centre for Global Health Research. Usher Institute. University of Edinburgh. Edinburgh, Scotland/ MRC Human Genetics Unit. Institute of Genetics and Cancer. University of Edinburgh. Edinburgh, Scotland.
Jørgen K Kanters
Laboratory of Experimental Cardiology. Department of Biomedical Sciences. University of Copenhagen. Copenhagen, Denmark.
Nona Sotoodehnia
Cardiovascular Health Research Unit. Division of Cardiology. Department of Medicine. University of Washington. Seattle, WA, USA.
Borbala Mifsud
William Harvey Research Institute. Clinical Pharmacology. Queen Mary University of London. London, UK/ Genomics and Translational Biomedicine. College of Health and Life Sciences. Hamad Bin Khalifa University. Doha, Qatar.
Pier D Lambiase
Barts Heart Centre. St Bartholomew's Hospital. Barts Health NHS trust. London, UK/Institute of Cardiovascular Sciences. University of College London. London, UK.
Larisa G Tereshchenko
Department of Quantitative Health Sciences. Lerner Research Institute. Cleveland Clinic. Cleveland, OH, USA/Department of Medicine. Cardiovascular Division. Johns Hopkins University. School of Medicine. Baltimore, MD, USA.
Patricia B Munroe
William Harvey Research Institute. Clinical Pharmacology. Queen Mary University of London. London, UK/NIHR Barts Cardiovascular Biomedical Research Centre. Barts and The London School of Medicine and Dentistry. Queen Mary University of London. London, UK.
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