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


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
14 03 2023
Historique:
received: 27 05 2022
accepted: 26 02 2023
entrez: 15 3 2023
pubmed: 16 3 2023
medline: 17 3 2023
Statut: epublish

Résumé

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.

Identifiants

pubmed: 36918541
doi: 10.1038/s41467-023-36997-w
pii: 10.1038/s41467-023-36997-w
pmc: PMC10015012
doi:

Substances chimiques

Biomarkers 0

Types de publication

Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1411

Subventions

Organisme : Medical Research Council
ID : MC_UU_00007/10
Pays : United Kingdom
Organisme : NHLBI NIH HHS
ID : R56 HL118277
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL105756
Pays : United States
Organisme : NHLBI NIH HHS
ID : R01 HL118277
Pays : United States
Organisme : NHLBI NIH HHS
ID : K24 HL148521
Pays : United States

Informations de copyright

© 2023. The Author(s).

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Auteurs

William J Young (WJ)

William Harvey Research Institute, Clinical Pharmacology, Queen Mary University of London, London, UK.
Barts Heart Centre, St Bartholomew's Hospital, Barts Health NHS trust, London, UK.

Jeffrey Haessler (J)

Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.

Jan-Walter Benjamins (JW)

University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands.

Linda Repetto (L)

Centre for Global Health Research, Usher Institute, University of Edinburgh, Edinburgh, Scotland.

Jie Yao (J)

Institute for Translational Genomics and Population Sciences/The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.

Aaron Isaacs (A)

Dept. of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands.
Maastricht Center for Systems Biology (MaCSBio), Maastricht University, Maastricht, the Netherlands.

Andrew R Harper (AR)

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 (J)

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 and Center of Biomedical Research Network, Bioengineering, Biomaterials and Nanomedicine, Zaragoza, Spain.

Sophie Garnier (S)

Sorbonne Universite, INSERM, UMR-S1166, Research Unit on Cardiovascular Disorders, Metabolism and Nutrition, Team Genomics & Pathophysiology of Cardiovascular Disease, Paris, 75013, France.
ICAN Institute for Cardiometabolism and Nutrition, Paris, 75013, France.

Stefan van Duijvenboden (S)

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 (AR)

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Maria Pina Concas (MP)

Institute for Maternal and Child Health - IRCCS "Burlo Garofolo", Trieste, Italy.

ThuyVy Duong (T)

McKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Luisa Foco (L)

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

Jonas L Isaksen (JL)

Laboratory of Experimental Cardiology, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.

Hao Mei (H)

Department of Data Science, University of Mississippi Medical Center, Jackson, MS, USA.

Raymond Noordam (R)

Department of Internal Medicine, section of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, the Netherlands.

Casia Nursyifa (C)

Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Anne Richmond (A)

MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, Scotland.

Meddly L Santolalla (ML)

Department of Genetics, Ecology and Evolution, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Emerge, Emerging Diseases and Climate Change Research Unit, School of Public Health and Administration, Universidad Peruana Cayetano Heredia, Lima, 15152, Peru.

Colleen M Sitlani (CM)

Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.

Negin Soroush (N)

Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.

Sébastien Thériault (S)

Population Health Research Institute, McMaster University, Hamilton, ON, Canada.
Department of Molecular Biology, Medical Biochemistry and Pathology, Université Laval, Quebec, QC, Canada.

Stella Trompet (S)

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 (S)

Cardiovascular Research Institute Basel, University Hospital Basel, University of Basel, Basel, Switzerland.

Fariba Ahmadizar (F)

Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.
Julius Global Health, University Utrecht Medical Center, Utrecht, the Netherlands.

Alvaro Alonso (A)

Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.

Jennifer A Brody (JA)

Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.

Archie Campbell (A)

Usher Institute, University of Edinburgh, Nine, Edinburgh Bioquarter, 9 Little France Road, Edinburgh, UK.
Health Data Research UK, University of Edinburgh, Nine, Edinburgh Bioquarter, 9 Little France Road, Edinburgh, UK.
Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, Edinburgh, UK.

Adolfo Correa (A)

Departments of Medicine, Pediatrics and Population Health Science, University of Mississippi Medical Center, Jackson, MS, USA.

Dawood Darbar (D)

Department of Medicine, University of Illinois at Chicago, Chicago, IL, USA.

Antonio De Luca (A)

Cardiothoracovascular Department, Division of Cardiology, Azienda Sanitaria Universitaria Giuliano Isontina and University of Trieste, Trieste, Italy.

Jean-François Deleuze (JF)

Université Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine (CNRGH), 91057, Evry, France.
Laboratory of Excellence GENMED (Medical Genomics), Paris, France.
Centre d'Etude du Polymorphisme Humain, Fondation Jean Dausset, Paris, France.

Christina Ellervik (C)

Department of Data and Data Support, Region Zealand, 4180, Sorø, Denmark.
Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, 2100, Copenhagen, Denmark.
Department of Laboratory Medicine, Boston Children's Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA, 02115, USA.

Christian Fuchsberger (C)

Eurac Research, Institute for Biomedicine (affiliated with the 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 (A)

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 (C)

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 (X)

Institute for Translational Genomics and Population Sciences/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 (T)

Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Susan R Heckbert (SR)

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 (RD)

Center for Clinical and Translational Science, Ohio State Medical Center, Columbus, OH, USA.

Jan A Kors (JA)

Department of Medical Informatics, Erasmus University Medical Center, Rotterdam, the Netherlands.

Maria Fernanda Lima-Costa (MF)

Instituto René Rachou, fundação Oswaldo Cruz, Belo Horizonte, Minas Gerais, Brazil.

Allan Linneberg (A)

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 (PW)

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 (AC)

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 (P)

MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, Scotland.

David J Porteous (DJ)

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 (PP)

Eurac Research, Institute for Biomedicine (affiliated with the University of Lübeck), Bolzano, Italy.
Department of Neurology, University of Lübeck, Lübeck, Germany.

Alexander P Reiner (AP)

Department of Epidemiology, University of Washington, Seattle, WA, USA.
Fred Hutchinson Cancer Center, University of Washington, Seattle, WA, USA.

Lorenz Risch (L)

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 (U)

Dept. of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands.

Xia Shen (X)

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 (Guangzhou), Fudan University, Nansha District, Guangzhou, China.

Gianfranco Sinagra (G)

Cardiothoracovascular Department, Division of Cardiology, Azienda Sanitaria Universitaria Giuliano Isontina and University of Trieste, Trieste, Italy.

Elsayed Z Soliman (EZ)

Epidemiological Cardiology Research Center (EPICARE), Wake Forest School of Medicine, Winston Salem, NC, USA.

Monika Stoll (M)

Maastricht Center for Systems Biology (MaCSBio), Maastricht University, Maastricht, the Netherlands.
Dept. of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, the Netherlands.
Institute of Human Genetics, Genetic Epidemiology, University of Muenster, Muenster, Germany.

Eduardo Tarazona-Santos (E)

Department of Genetics, Ecology and Evolution, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.

Andrew Tinker (A)

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 (K)

Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands.

Eric Villard (E)

Sorbonne Universite, INSERM, UMR-S1166, Research Unit on Cardiovascular Disorders, Metabolism and Nutrition, Team Genomics & Pathophysiology of Cardiovascular Disease, Paris, 75013, France.
ICAN Institute for Cardiometabolism and Nutrition, Paris, 75013, France.

Helen R Warren (HR)

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 (EA)

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, 27599, USA.

Kerri L Wiggins (KL)

Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.

Dan E Arking (DE)

McKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Christy L Avery (CL)

Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

David Conen (D)

Population Health Research Institute, McMaster University, Hamilton, ON, Canada.

Giorgia Girotto (G)

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 (N)

Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Caroline Hayward (C)

MRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Western General Hospital, Edinburgh, UK.

J Wouter Jukema (JW)

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 (DO)

Department of Clinical Epidemiology, Leiden University Medical Center, Leiden, the Netherlands, Leiden, the Netherlands.
Department of Public Health and Primary Care, Leiden University Medical Center, Leiden, the Netherlands, Leiden, the Netherlands.

Morten Salling Olesen (MS)

Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.

Sandosh Padmanabhan (S)

Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, UK.

Bruce M Psaty (BM)

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 (C)

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

Antonio Luiz P Ribeiro (ALP)

Department of Internal Medicine, Faculdade de Medicina, Universidade Federal de Minas Gerais, Brazil, Belo Horizonte, Minas Gerais, Brazil.
Cardiology Service and Telehealth Center, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil, Belo Horizonte, Minas Gerais, Brazil.

Jerome I Rotter (JI)

Institute for Translational Genomics and Population Sciences/The Lundquist Institute at Harbor-UCLA Medical Center, Torrance, CA, USA.
Department of Pediatrics, Harbor-UCLA Medical Center, Torrance, CA, USA.
Departments of Pediatrics and Human Genetics, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.

Bruno H Stricker (BH)

Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands.

Pim van der Harst (P)

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 (CM)

Nuffield Department of Population Health, University of Oxford, Oxford, UK.
Department of Epidemiology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.

Niek Verweij (N)

University of Groningen, University Medical Center Groningen, Department of Cardiology, Groningen, the Netherlands.

James G Wilson (JG)

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 (M)

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 (P)

Sorbonne Universite, INSERM, UMR-S1166, Research Unit on Cardiovascular Disorders, Metabolism and Nutrition, Team Genomics & Pathophysiology of Cardiovascular Disease, Paris, 75013, France.
ICAN Institute for Cardiometabolism and Nutrition, Paris, 75013, France.
APHP, Cardiology Department, Pitié-Salpêtrière Hospital, Paris, 75013, France.
APHP, Département de Génétique, Centre de Référence Maladies Cardiaques Héréditaires, Pitié-Salpêtrière Hospital, Paris, 75013, France.

Hugh Watkins (H)

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 (C)

Public Health Sciences Division, Fred Hutchinson Cancer Center, Seattle, WA, USA.

Henry J Lin (HJ)

Institute for Translational Genomics and Population Sciences/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 (JF)

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 (JK)

Laboratory of Experimental Cardiology, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.

Nona Sotoodehnia (N)

Cardiovascular Health Research Unit, Division of Cardiology, Department of Medicine, University of Washington, Seattle, WA, USA.

Borbala Mifsud (B)

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 (PD)

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 (LG)

Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, OH, USA. tereshl@ccf.org.
Department of Medicine, Cardiovascular Division, Johns Hopkins University, School of Medicine, Baltimore, MD, USA. tereshl@ccf.org.

Patricia B Munroe (PB)

William Harvey Research Institute, Clinical Pharmacology, Queen Mary University of London, London, UK. p.b.munroe@qmul.ac.uk.
NIHR Barts Cardiovascular Biomedical Research Centre, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London, UK. p.b.munroe@qmul.ac.uk.

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