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Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease

Author

Listed:
  • William J. Young

    (Queen Mary University of London
    St Bartholomew’s Hospital, Barts Health NHS trust)

  • Jeffrey Haessler

    (Fred Hutchinson Cancer Center)

  • Jan-Walter Benjamins

    (University of Groningen, University Medical Center Groningen, Department of Cardiology)

  • Linda Repetto

    (Usher Institute, University of Edinburgh)

  • Jie Yao

    (Institute for Translational Genomics and Population Sciences/The Lundquist Institute at Harbor-UCLA Medical Center)

  • Aaron Isaacs

    (Cardiovascular Research Institute Maastricht (CARIM), Maastricht University
    Maastricht University)

  • Andrew R. Harper

    (University of Oxford, Division of Cardiovascular Medicine, John Radcliffe Hospital
    Wellcome Centre for Human Genetics, Roosevelt Drive)

  • Julia Ramirez

    (Queen Mary University of London
    University of College London
    University of Zaragoza, Zaragoza, Spain and Center of Biomedical Research Network, Bioengineering, Biomaterials and Nanomedicine)

  • Sophie Garnier

    (Sorbonne Universite, INSERM, UMR-S1166, Research Unit on Cardiovascular Disorders, Metabolism and Nutrition, Team Genomics & Pathophysiology of Cardiovascular Disease
    ICAN Institute for Cardiometabolism and Nutrition)

  • Stefan Duijvenboden

    (Queen Mary University of London
    University of College London)

  • Antoine R. Baldassari

    (University of North Carolina at Chapel Hill)

  • Maria Pina Concas

    (Institute for Maternal and Child Health – IRCCS “Burlo Garofolo”)

  • ThuyVy Duong

    (Johns Hopkins University School of Medicine)

  • Luisa Foco

    (Eurac Research, Institute for Biomedicine (affiliated with the University of Lübeck))

  • Jonas L. Isaksen

    (University of Copenhagen)

  • Hao Mei

    (University of Mississippi Medical Center)

  • Raymond Noordam

    (Leiden University Medical Center)

  • Casia Nursyifa

    (University of Copenhagen)

  • Anne Richmond

    (University of Edinburgh)

  • Meddly L. Santolalla

    (Universidade Federal de Minas Gerais
    Universidad Peruana Cayetano Heredia)

  • Colleen M. Sitlani

    (University of Washington)

  • Negin Soroush

    (Erasmus Medical Center)

  • Sébastien Thériault

    (Population Health Research Institute, McMaster University
    Université Laval)

  • Stella Trompet

    (Leiden University Medical Center
    Leiden University Medical Center)

  • Stefanie Aeschbacher

    (University Hospital Basel, University of Basel)

  • Fariba Ahmadizar

    (Erasmus Medical Center
    University Utrecht Medical Center)

  • Alvaro Alonso

    (Rollins School of Public Health, Emory University)

  • Jennifer A. Brody

    (University of Washington)

  • Archie Campbell

    (Usher Institute, University of Edinburgh
    University of Edinburgh
    Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital)

  • Adolfo Correa

    (University of Mississippi Medical Center)

  • Dawood Darbar

    (University of Illinois at Chicago)

  • Antonio Luca

    (Azienda Sanitaria Universitaria Giuliano Isontina and University of Trieste)

  • Jean-François Deleuze

    (Université Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine (CNRGH)
    Laboratory of Excellence GENMED (Medical Genomics)
    Centre d’Etude du Polymorphisme Humain, Fondation Jean Dausset)

  • Christina Ellervik

    (Department of Data and Data Support, Region Zealand
    University of Copenhagen
    Boston Children’s Hospital, Harvard Medical School)

  • Christian Fuchsberger

    (Eurac Research, Institute for Biomedicine (affiliated with the University of Lübeck)
    University of Michigan School of Public Health
    University of Michigan School of Public Health)

  • Anuj Goel

    (University of Oxford, Division of Cardiovascular Medicine, John Radcliffe Hospital
    Wellcome Centre for Human Genetics, Roosevelt Drive)

  • Christopher Grace

    (University of Oxford, Division of Cardiovascular Medicine, John Radcliffe Hospital
    Wellcome Centre for Human Genetics, Roosevelt Drive)

  • Xiuqing Guo

    (Institute for Translational Genomics and Population Sciences/The Lundquist Institute at Harbor-UCLA Medical Center
    Harbor-UCLA Medical Center
    David Geffen School of Medicine at UCLA)

  • Torben Hansen

    (University of Copenhagen)

  • Susan R. Heckbert

    (University of Washington
    University of Washington)

  • Rebecca D. Jackson

    (Ohio State Medical Center)

  • Jan A. Kors

    (Erasmus University Medical Center)

  • Maria Fernanda Lima-Costa

    (Instituto René Rachou, fundação Oswaldo Cruz)

  • Allan Linneberg

    (Bispebjerg and Frederiksberg Hospital
    University of Copenhagen)

  • Peter W. Macfarlane

    (University of Glasgow)

  • Alanna C. Morrison

    (The University of Texas Health Science Center at Houston)

  • Pau Navarro

    (University of Edinburgh)

  • David J. Porteous

    (Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital
    University of Edinburgh)

  • Peter P. Pramstaller

    (Eurac Research, Institute for Biomedicine (affiliated with the University of Lübeck)
    University of Lübeck)

  • Alexander P. Reiner

    (University of Washington
    University of Washington)

  • Lorenz Risch

    (Labormedizinisches zentrum Dr. Risch
    Private University in the Principality of Liechtenstein
    University Institute of Clinical Chemistry, University of Bern, Inselspital)

  • Ulrich Schotten

    (Cardiovascular Research Institute Maastricht (CARIM), Maastricht University)

  • Xia Shen

    (Usher Institute, University of Edinburgh
    Karolinska Institutet
    Fudan University, Nansha District)

  • Gianfranco Sinagra

    (Azienda Sanitaria Universitaria Giuliano Isontina and University of Trieste)

  • Elsayed Z. Soliman

    (Wake Forest School of Medicine)

  • Monika Stoll

    (Maastricht University
    Maastricht University
    University of Muenster)

  • Eduardo Tarazona-Santos

    (Universidade Federal de Minas Gerais)

  • Andrew Tinker

    (Queen Mary University of London
    Queen Mary University of London)

  • Katerina Trajanoska

    (Erasmus Medical Center)

  • Eric Villard

    (Sorbonne Universite, INSERM, UMR-S1166, Research Unit on Cardiovascular Disorders, Metabolism and Nutrition, Team Genomics & Pathophysiology of Cardiovascular Disease
    ICAN Institute for Cardiometabolism and Nutrition)

  • Helen R. Warren

    (Queen Mary University of London
    Queen Mary University of London)

  • Eric A. Whitsel

    (University of North Carolina at Chapel Hill
    University of North Carolina)

  • Kerri L. Wiggins

    (University of Washington)

  • Dan E. Arking

    (Johns Hopkins University School of Medicine)

  • Christy L. Avery

    (University of North Carolina at Chapel Hill)

  • David Conen

    (Population Health Research Institute, McMaster University)

  • Giorgia Girotto

    (Institute for Maternal and Child Health – IRCCS “Burlo Garofolo”
    University of Trieste)

  • Niels Grarup

    (University of Copenhagen)

  • Caroline Hayward

    (University of Edinburgh, Western General Hospital)

  • J.Wouter Jukema

    (Leiden University Medical Center
    Netherlands Heart Institute
    Durrer Center for Cardiovascular Research)

  • Dennis O. Mook-Kanamori

    (Leiden University Medical Center, Leiden, the Netherlands
    Leiden University Medical Center, Leiden, the Netherlands)

  • Morten Salling Olesen

    (University of Copenhagen)

  • Sandosh Padmanabhan

    (University of Glasgow)

  • Bruce M. Psaty

    (University of Washington
    University of Washington
    University of Washington)

  • Cristian Pattaro

    (Eurac Research, Institute for Biomedicine (affiliated with the University of Lübeck))

  • Antonio Luiz P. Ribeiro

    (Universidade Federal de Minas Gerais, Brazil
    Universidade Federal de Minas Gerais, Belo Horizonte, Brazil)

  • Jerome I. Rotter

    (Institute for Translational Genomics and Population Sciences/The Lundquist Institute at Harbor-UCLA Medical Center
    Harbor-UCLA Medical Center
    David Geffen School of Medicine at UCLA)

  • Bruno H. Stricker

    (Erasmus Medical Center)

  • Pim Harst

    (University of Groningen, University Medical Center Groningen, Department of Cardiology
    University Medical Center Utrecht)

  • Cornelia M. Duijn

    (University of Oxford
    Erasmus MC University Medical Center)

  • Niek Verweij

    (University of Groningen, University Medical Center Groningen, Department of Cardiology)

  • James G. Wilson

    (University of Mississippi Medical Center
    Beth Israel Deaconess Medical Center)

  • Michele Orini

    (St Bartholomew’s Hospital, Barts Health NHS trust
    University of College London)

  • Philippe Charron

    (Sorbonne Universite, INSERM, UMR-S1166, Research Unit on Cardiovascular Disorders, Metabolism and Nutrition, Team Genomics & Pathophysiology of Cardiovascular Disease
    ICAN Institute for Cardiometabolism and Nutrition
    Pitié-Salpêtrière Hospital
    Centre de Référence Maladies Cardiaques Héréditaires, Pitié-Salpêtrière Hospital)

  • Hugh Watkins

    (University of Oxford, Division of Cardiovascular Medicine, John Radcliffe Hospital
    Wellcome Centre for Human Genetics, Roosevelt Drive)

  • Charles Kooperberg

    (Fred Hutchinson Cancer Center)

  • Henry J. Lin

    (Institute for Translational Genomics and Population Sciences/The Lundquist Institute at Harbor-UCLA Medical Center
    Harbor-UCLA Medical Center
    David Geffen School of Medicine at UCLA)

  • James F. Wilson

    (Usher Institute, University of Edinburgh
    University of Edinburgh)

  • Jørgen K. Kanters

    (University of Copenhagen)

  • Nona Sotoodehnia

    (University of Washington)

  • Borbala Mifsud

    (Queen Mary University of London
    College of Health and Life Sciences, Hamad Bin Khalifa University)

  • Pier D. Lambiase

    (St Bartholomew’s Hospital, Barts Health NHS trust
    University of College London)

  • Larisa G. Tereshchenko

    (Lerner Research Institute, Cleveland Clinic
    Johns Hopkins University, School of Medicine)

  • Patricia B. Munroe

    (Queen Mary University of London
    Queen Mary University of London)

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.

Suggested Citation

  • William J. Young & Jeffrey Haessler & Jan-Walter Benjamins & Linda Repetto & Jie Yao & Aaron Isaacs & Andrew R. Harper & Julia Ramirez & Sophie Garnier & Stefan Duijvenboden & Antoine R. Baldassari & , 2023. "Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36997-w
    DOI: 10.1038/s41467-023-36997-w
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