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

• Type of Material: Article
• Authors: William J Young, Barts and The London School of Medicine and Dentistry; Jeffrey Haessler, Fred Hutchinson Cancer Research Center; Jan-Walter Benjamins, Universitair Medisch Centrum Groningen; Linda Repetto, Edinburgh Medical School; Jie Yao, Harbor-UCLA Medical Center; Aaron Isaacs, CARIM School for Cardiovascular Disease; Andrew R Harper, University of Oxford Medical Sciences Division; Julia Ramirez, Barts and The London School of Medicine and Dentistry; Sophie Garnier, Sorbonne Université; Stefan van Duijvenboden, Barts and The London School of Medicine and Dentistry; Antoine R Baldassari, The University of North Carolina at Chapel Hill; Maria Pina Concas, Institute for Maternal and Child Health – IRCCS “Burlo Garofolo”, Trieste, Italy; ThuyVy V Duong, Johns Hopkins School of Medicine; Luisa Foco, EURAC Research, Institute for Biomedicine; 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; Collen M Sitlani, University of Washington School of Medicine; Negin Soroush, Erasmus Medical Center; Sébastien Thériault, McMaster University; Stella Trompet, Leids Universitair Medisch Centrum; Stefanie Aeschbacher, University of Basel; Fariba Ahmadizar, Erasmus Medical Center; Alvaro Alonso, Emory University; Jennifer A Brody, University of Washington School of Medicine; Archie Campbell, Edinburgh Medical School; Adolfo Correa, Emory University; Dawood Darbar, University of Illinois at Chicago; Antonio De Luca, Azienda Sanitaria Universitaria Giuliano Isontina; Jean-François Deleuze, Centre National de Recherche en Génomique Humaine; Christina Ellervik, Region Zealand; Christian Fuchsberger, EURAC Research, Institute for Biomedicine; Anuj Goel, University of Oxford Medical Sciences Division; Christopher Grace, University of Oxford Medical Sciences Division; Xiuqing Guo, Harbor-UCLA Medical Center; Torben Hansen, Novo Nordisk Foundation Center for Basic Metabolic Research; Susan R Heckbert, University of Washington School of Medicine; Rebecca D Jackson, The Ohio State University Wexner Medical Center; Jan A Kors, Erasmus Medical Center; Maria Fernanda Lima-Costa, Fundacao Oswaldo Cruz; Allan Linneberg, Frederiksberg Hospital; Peter W Macfarlane, University of Glasgow; Alanna C Morrison, University of Texas School of Public Health; Pau Navarro, University of Edinburgh; David J Porteous, University of Edinburgh; Peter P Pramstaller, EURAC Research, Institute for Biomedicine; Alexander P Reiner, University of Washington; Lorenz Risch, Labormedizinisches Zentrum Dr. Risch; Ulrich Schotten, CARIM School for Cardiovascular Disease; Xia Shen, Edinburgh Medical School; Gianfranco Sinagra, Azienda Sanitaria Universitaria Giuliano Isontina; Elsayed Z Soliman, Wake Forest University School of Medicine; Monika Stoll, Universiteit Maastricht; Eduardo Tarazona-Santos, Universidade Federal de Minas Gerais; Andrew Tinker, Barts and The London School of Medicine and Dentistry; Katerina Trajanoska, Erasmus Medical Center; Eric Villard, Sorbonne Université; Helen R Warren, Barts and The London School of Medicine and Dentistry; Eric A Whitsel, The University of North Carolina at Chapel Hill; Kerri L Wiggins, University of Washington School of Medicine; Dan E Arking, Johns Hopkins School of Medicine; Christy L Avery, The University of North Carolina at Chapel Hill; David Conen, Population Health Research Institute, Ontario; Giorgia Girotto, IRCCS Burlo Garofolo; Niels Grarup, Novo Nordisk Foundation Center for Basic Metabolic Research; Caroline Hayward, MRC Human Genetics Unit; Wouter J Jukema, Leids Universitair Medisch Centrum; Dennis O Mook-Kanamori, Leids Universitair Medisch Centrum; Morten Salling Olesen, Københavns Universitet; Sandosh Padmanabhan, College of Medical, Veterinary & Life Sciences; Bruce M Psaty, University of Washington School of Medicine; Cristian Pattaro, EURAC Research, Institute for Biomedicine; Antonio Luiz P Ribeiro, Universidade Federal de Minas Gerais; Jerome I Rotter, Harbor-UCLA Medical Center; Bruno H Stricker, Erasmus MC; Pim van der Harst, Universitair Medisch Centrum Groningen; Cornelia M van Duijn, University of Oxford Medical Sciences Division; Niek Verweij, Universitair Medisch Centrum Groningen; James G Wilson, University of Mississippi Medical Center; Michele Orini, St Bartholomew's Hospital; Philippe Charron, Sorbonne Université; Hugh Watkins, University of Oxford Medical Sciences Division; Charles Kooperberg, Fred Hutchinson Cancer Research Center; Henry J Lin, Harbor-UCLA Medical Center; James F Wilson, Edinburgh Medical School; Jørgen K Kanters, Københavns Universitet; Nona Sotoodehnia, University of Washington School of Medicine; Borbala Mifsud, Barts and The London School of Medicine and Dentistry; Pier D Lambiase, St Bartholomew's Hospital; Larisa G Tereshchenko, Cleveland Clinic Foundation; Patricia B Munroe, Barts and The London School of Medicine and Dentistry
• Language: English
• Date: 2023-12-01
• Publisher: Emory University Libraries
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2023
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s41467-023-36997-w
• Title of Journal or Parent Work: Nature Communications
• Volume: 14
• Issue: 1
• Start Page: 1411
• End Page: 1411
• Keywords: Cardiovascular Diseases; Arrhythmias, Cardiac; Atrioventricular Block; Biomarkers; Risk Factors; Electrocardiography; Humans; Genome-Wide Association Study
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Pharmacology; Health Sciences, Epidemiology; Health Sciences, Public Health

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.