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

The spatial and frontal QRS-T angles are electrocardiographic (ECG) predictors for arrhythmia. This work used genetic analyses to identify associated loci and pathways, and explore their relationships with other ECG traits and cardiovascular disease.

Bibliographic Details
Main Authors: William J. Young, Jeffrey Haessler, Jan-Walter Benjamins, Linda Repetto, Jie Yao, Aaron Isaacs, Andrew R. Harper, Julia Ramirez, Sophie Garnier, Stefan van Duijvenboden, Antoine R. Baldassari, Maria Pina Concas, ThuyVy Duong, Luisa Foco, Jonas L. Isaksen, Hao Mei, Raymond Noordam, Casia Nursyifa, Anne Richmond, Meddly L. Santolalla, Colleen M. Sitlani, Negin Soroush, Sébastien Thériault, Stella Trompet, Stefanie Aeschbacher, Fariba Ahmadizar, Alvaro Alonso, Jennifer A. Brody, Archie Campbell, Adolfo Correa, Dawood Darbar, Antonio De Luca, Jean-François Deleuze, Christina Ellervik, Christian Fuchsberger, Anuj Goel, Christopher Grace, Xiuqing Guo, Torben Hansen, Susan R. Heckbert, Rebecca D. Jackson, Jan A. Kors, Maria Fernanda Lima-Costa, Allan Linneberg, Peter W. Macfarlane, Alanna C. Morrison, Pau Navarro, David J. Porteous, Peter P. Pramstaller, Alexander P. Reiner, Lorenz Risch, Ulrich Schotten, Xia Shen, Gianfranco Sinagra, Elsayed Z. Soliman, Monika Stoll, Eduardo Tarazona-Santos, Andrew Tinker, Katerina Trajanoska, Eric Villard, Helen R. Warren, Eric A. Whitsel, Kerri L. Wiggins, Dan E. Arking, Christy L. Avery, David Conen, Giorgia Girotto, Niels Grarup, Caroline Hayward, J.Wouter Jukema, Dennis O. Mook-Kanamori, Morten Salling Olesen, Sandosh Padmanabhan, Bruce M. Psaty, Cristian Pattaro, Antonio Luiz P. Ribeiro, Jerome I. Rotter, Bruno H. Stricker, Pim van der Harst, Cornelia M. van Duijn, Niek Verweij, James G. Wilson, Michele Orini, Philippe Charron, Hugh Watkins, Charles Kooperberg, Henry J. Lin, James F. Wilson, Jørgen K. Kanters, Nona Sotoodehnia, Borbala Mifsud, Pier D. Lambiase, Larisa G. Tereshchenko, Patricia B. Munroe
Format: Article
Language:English
Published: Nature Portfolio 2023-03-01
Series:Nature Communications
Online Access:https://doi.org/10.1038/s41467-023-36997-w
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author William J. Young
Jeffrey Haessler
Jan-Walter Benjamins
Linda Repetto
Jie Yao
Aaron Isaacs
Andrew R. Harper
Julia Ramirez
Sophie Garnier
Stefan van Duijvenboden
Antoine R. Baldassari
Maria Pina Concas
ThuyVy Duong
Luisa Foco
Jonas L. Isaksen
Hao Mei
Raymond Noordam
Casia Nursyifa
Anne Richmond
Meddly L. Santolalla
Colleen M. Sitlani
Negin Soroush
Sébastien Thériault
Stella Trompet
Stefanie Aeschbacher
Fariba Ahmadizar
Alvaro Alonso
Jennifer A. Brody
Archie Campbell
Adolfo Correa
Dawood Darbar
Antonio De Luca
Jean-François Deleuze
Christina Ellervik
Christian Fuchsberger
Anuj Goel
Christopher Grace
Xiuqing Guo
Torben Hansen
Susan R. Heckbert
Rebecca D. Jackson
Jan A. Kors
Maria Fernanda Lima-Costa
Allan Linneberg
Peter W. Macfarlane
Alanna C. Morrison
Pau Navarro
David J. Porteous
Peter P. Pramstaller
Alexander P. Reiner
Lorenz Risch
Ulrich Schotten
Xia Shen
Gianfranco Sinagra
Elsayed Z. Soliman
Monika Stoll
Eduardo Tarazona-Santos
Andrew Tinker
Katerina Trajanoska
Eric Villard
Helen R. Warren
Eric A. Whitsel
Kerri L. Wiggins
Dan E. Arking
Christy L. Avery
David Conen
Giorgia Girotto
Niels Grarup
Caroline Hayward
J.Wouter Jukema
Dennis O. Mook-Kanamori
Morten Salling Olesen
Sandosh Padmanabhan
Bruce M. Psaty
Cristian Pattaro
Antonio Luiz P. Ribeiro
Jerome I. Rotter
Bruno H. Stricker
Pim van der Harst
Cornelia M. van Duijn
Niek Verweij
James G. Wilson
Michele Orini
Philippe Charron
Hugh Watkins
Charles Kooperberg
Henry J. Lin
James F. Wilson
Jørgen K. Kanters
Nona Sotoodehnia
Borbala Mifsud
Pier D. Lambiase
Larisa G. Tereshchenko
Patricia B. Munroe
author_facet William J. Young
Jeffrey Haessler
Jan-Walter Benjamins
Linda Repetto
Jie Yao
Aaron Isaacs
Andrew R. Harper
Julia Ramirez
Sophie Garnier
Stefan van Duijvenboden
Antoine R. Baldassari
Maria Pina Concas
ThuyVy Duong
Luisa Foco
Jonas L. Isaksen
Hao Mei
Raymond Noordam
Casia Nursyifa
Anne Richmond
Meddly L. Santolalla
Colleen M. Sitlani
Negin Soroush
Sébastien Thériault
Stella Trompet
Stefanie Aeschbacher
Fariba Ahmadizar
Alvaro Alonso
Jennifer A. Brody
Archie Campbell
Adolfo Correa
Dawood Darbar
Antonio De Luca
Jean-François Deleuze
Christina Ellervik
Christian Fuchsberger
Anuj Goel
Christopher Grace
Xiuqing Guo
Torben Hansen
Susan R. Heckbert
Rebecca D. Jackson
Jan A. Kors
Maria Fernanda Lima-Costa
Allan Linneberg
Peter W. Macfarlane
Alanna C. Morrison
Pau Navarro
David J. Porteous
Peter P. Pramstaller
Alexander P. Reiner
Lorenz Risch
Ulrich Schotten
Xia Shen
Gianfranco Sinagra
Elsayed Z. Soliman
Monika Stoll
Eduardo Tarazona-Santos
Andrew Tinker
Katerina Trajanoska
Eric Villard
Helen R. Warren
Eric A. Whitsel
Kerri L. Wiggins
Dan E. Arking
Christy L. Avery
David Conen
Giorgia Girotto
Niels Grarup
Caroline Hayward
J.Wouter Jukema
Dennis O. Mook-Kanamori
Morten Salling Olesen
Sandosh Padmanabhan
Bruce M. Psaty
Cristian Pattaro
Antonio Luiz P. Ribeiro
Jerome I. Rotter
Bruno H. Stricker
Pim van der Harst
Cornelia M. van Duijn
Niek Verweij
James G. Wilson
Michele Orini
Philippe Charron
Hugh Watkins
Charles Kooperberg
Henry J. Lin
James F. Wilson
Jørgen K. Kanters
Nona Sotoodehnia
Borbala Mifsud
Pier D. Lambiase
Larisa G. Tereshchenko
Patricia B. Munroe
author_sort William J. Young
collection DOAJ
description The spatial and frontal QRS-T angles are electrocardiographic (ECG) predictors for arrhythmia. This work used genetic analyses to identify associated loci and pathways, and explore their relationships with other ECG traits and cardiovascular disease.
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spelling doaj.art-dafca92a55c441c48a99162ccb2f32052023-03-22T11:47:39ZengNature PortfolioNature Communications2041-17232023-03-0114111610.1038/s41467-023-36997-wGenetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular diseaseWilliam J. Young0Jeffrey Haessler1Jan-Walter Benjamins2Linda Repetto3Jie Yao4Aaron Isaacs5Andrew R. Harper6Julia Ramirez7Sophie Garnier8Stefan van Duijvenboden9Antoine R. Baldassari10Maria Pina Concas11ThuyVy Duong12Luisa Foco13Jonas L. Isaksen14Hao Mei15Raymond Noordam16Casia Nursyifa17Anne Richmond18Meddly L. Santolalla19Colleen M. Sitlani20Negin Soroush21Sébastien Thériault22Stella Trompet23Stefanie Aeschbacher24Fariba Ahmadizar25Alvaro Alonso26Jennifer A. Brody27Archie Campbell28Adolfo Correa29Dawood Darbar30Antonio De Luca31Jean-François Deleuze32Christina Ellervik33Christian Fuchsberger34Anuj Goel35Christopher Grace36Xiuqing Guo37Torben Hansen38Susan R. Heckbert39Rebecca D. Jackson40Jan A. Kors41Maria Fernanda Lima-Costa42Allan Linneberg43Peter W. Macfarlane44Alanna C. Morrison45Pau Navarro46David J. Porteous47Peter P. Pramstaller48Alexander P. Reiner49Lorenz Risch50Ulrich Schotten51Xia Shen52Gianfranco Sinagra53Elsayed Z. Soliman54Monika Stoll55Eduardo Tarazona-Santos56Andrew Tinker57Katerina Trajanoska58Eric Villard59Helen R. Warren60Eric A. Whitsel61Kerri L. Wiggins62Dan E. Arking63Christy L. Avery64David Conen65Giorgia Girotto66Niels Grarup67Caroline Hayward68J.Wouter Jukema69Dennis O. Mook-Kanamori70Morten Salling Olesen71Sandosh Padmanabhan72Bruce M. Psaty73Cristian Pattaro74Antonio Luiz P. Ribeiro75Jerome I. Rotter76Bruno H. Stricker77Pim van der Harst78Cornelia M. van Duijn79Niek Verweij80James G. Wilson81Michele Orini82Philippe Charron83Hugh Watkins84Charles Kooperberg85Henry J. Lin86James F. Wilson87Jørgen K. Kanters88Nona Sotoodehnia89Borbala Mifsud90Pier D. Lambiase91Larisa G. Tereshchenko92Patricia B. Munroe93William Harvey Research Institute, Clinical Pharmacology, Queen Mary University of LondonPublic Health Sciences Division, Fred Hutchinson Cancer CenterUniversity of Groningen, University Medical Center Groningen, Department of CardiologyCentre for Global Health Research, Usher Institute, University of EdinburghInstitute for Translational Genomics and Population Sciences/The Lundquist Institute at Harbor-UCLA Medical CenterDept. of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht UniversityRadcliffe Department of Medicine, University of Oxford, Division of Cardiovascular Medicine, John Radcliffe HospitalWilliam Harvey Research Institute, Clinical Pharmacology, Queen Mary University of LondonSorbonne Universite, INSERM, UMR-S1166, Research Unit on Cardiovascular Disorders, Metabolism and Nutrition, Team Genomics & Pathophysiology of Cardiovascular DiseaseWilliam Harvey Research Institute, Clinical Pharmacology, Queen Mary University of LondonDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel HillInstitute for Maternal and Child Health – IRCCS “Burlo Garofolo”McKusick‐Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of MedicineEurac Research, Institute for Biomedicine (affiliated with the University of Lübeck)Laboratory of Experimental Cardiology, Department of Biomedical Sciences, University of CopenhagenDepartment of Data Science, University of Mississippi Medical CenterDepartment of Internal Medicine, section of Gerontology and Geriatrics, Leiden University Medical CenterNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of CopenhagenMRC Human Genetics Unit, Institute of Genetics and Cancer, University of EdinburghDepartment of Genetics, Ecology and Evolution, Instituto de Ciências Biológicas, Universidade Federal de Minas GeraisCardiovascular Health Research Unit, Department of Medicine, University of WashingtonDepartment of Epidemiology, Erasmus Medical CenterPopulation Health Research Institute, McMaster UniversityDepartment of Internal Medicine, section of Gerontology and Geriatrics, Leiden University Medical CenterCardiovascular Research Institute Basel, University Hospital Basel, University of BaselDepartment of Epidemiology, Erasmus Medical CenterDepartment of Epidemiology, Rollins School of Public Health, Emory UniversityCardiovascular Health Research Unit, Department of Medicine, University of WashingtonUsher Institute, University of EdinburghDepartments of Medicine, Pediatrics and Population Health Science, University of Mississippi Medical CenterDepartment of Medicine, University of Illinois at ChicagoCardiothoracovascular Department, Division of Cardiology, Azienda Sanitaria Universitaria Giuliano Isontina and University of TriesteUniversité Paris-Saclay, CEA, Centre National de Recherche en Génomique Humaine (CNRGH)Department of Data and Data Support, Region ZealandEurac Research, Institute for Biomedicine (affiliated with the University of Lübeck)Radcliffe Department of Medicine, University of Oxford, Division of Cardiovascular Medicine, John Radcliffe HospitalRadcliffe Department of Medicine, University of Oxford, Division of Cardiovascular Medicine, John Radcliffe HospitalInstitute for Translational Genomics and Population Sciences/The Lundquist Institute at Harbor-UCLA Medical CenterNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of CopenhagenCardiovascular Health Research Unit, Department of Medicine, University of WashingtonCenter for Clinical and Translational Science, Ohio State Medical CenterDepartment of Medical Informatics, Erasmus University Medical CenterInstituto René Rachou, fundação Oswaldo CruzCenter for Clinical Research and Prevention, Bispebjerg and Frederiksberg HospitalInstitute of Health and Wellbeing, School of Health and Wellbeing, College of Medical, Veterinary and Life Sciences, University of GlasgowHuman Genetics Center, Department of Epidemiology, Human Genetics, and Environmental Sciences, School of Public Health, The University of Texas Health Science Center at HoustonMRC Human Genetics Unit, Institute of Genetics and Cancer, University of EdinburghCentre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Western General HospitalEurac Research, Institute for Biomedicine (affiliated with the University of Lübeck)Department of Epidemiology, University of WashingtonLabormedizinisches zentrum Dr. RischDept. of Physiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht UniversityCentre for Global Health Research, Usher Institute, University of EdinburghCardiothoracovascular Department, Division of Cardiology, Azienda Sanitaria Universitaria Giuliano Isontina and University of TriesteEpidemiological Cardiology Research Center (EPICARE), Wake Forest School of MedicineMaastricht Center for Systems Biology (MaCSBio), Maastricht UniversityDepartment of Genetics, Ecology and Evolution, Instituto de Ciências Biológicas, Universidade Federal de Minas GeraisWilliam Harvey Research Institute, Clinical Pharmacology, Queen Mary University of LondonDepartment of Internal Medicine, Erasmus Medical CenterSorbonne Universite, INSERM, UMR-S1166, Research Unit on Cardiovascular Disorders, Metabolism and Nutrition, Team Genomics & Pathophysiology of Cardiovascular DiseaseWilliam Harvey Research Institute, Clinical Pharmacology, Queen Mary University of LondonDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel HillCardiovascular Health Research Unit, Department of Medicine, University of WashingtonMcKusick‐Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of MedicineDepartment of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel HillPopulation Health Research Institute, McMaster UniversityInstitute for Maternal and Child Health – IRCCS “Burlo Garofolo”Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of CopenhagenMRC Human Genetics Unit, Institute of Genetics and Cancer, University of Edinburgh, Western General HospitalDepartment of Cardiology, Leiden University Medical CenterDepartment of Clinical Epidemiology, Leiden University Medical Center, Leiden, the NetherlandsDepartment of Biomedical Sciences, University of CopenhagenInstitute of Cardiovascular and Medical Sciences, University of GlasgowCardiovascular Health Research Unit, Department of Medicine, University of WashingtonEurac Research, Institute for Biomedicine (affiliated with the University of Lübeck)Department of Internal Medicine, Faculdade de Medicina, Universidade Federal de Minas Gerais, BrazilInstitute for Translational Genomics and Population Sciences/The Lundquist Institute at Harbor-UCLA Medical CenterDepartment of Epidemiology, Erasmus Medical CenterUniversity of Groningen, University Medical Center Groningen, Department of CardiologyNuffield Department of Population Health, University of OxfordUniversity of Groningen, University Medical Center Groningen, Department of CardiologyDepartment of Physiology and Biophysics, University of Mississippi Medical CenterBarts Heart Centre, St Bartholomew’s Hospital, Barts Health NHS trustSorbonne Universite, INSERM, UMR-S1166, Research Unit on Cardiovascular Disorders, Metabolism and Nutrition, Team Genomics & Pathophysiology of Cardiovascular DiseaseRadcliffe Department of Medicine, University of Oxford, Division of Cardiovascular Medicine, John Radcliffe HospitalPublic Health Sciences Division, Fred Hutchinson Cancer CenterInstitute for Translational Genomics and Population Sciences/The Lundquist Institute at Harbor-UCLA Medical CenterCentre for Global Health Research, Usher Institute, University of EdinburghLaboratory of Experimental Cardiology, Department of Biomedical Sciences, University of CopenhagenCardiovascular Health Research Unit, Division of Cardiology, Department of Medicine, University of WashingtonWilliam Harvey Research Institute, Clinical Pharmacology, Queen Mary University of LondonBarts Heart Centre, St Bartholomew’s Hospital, Barts Health NHS trustDepartment of Quantitative Health Sciences, Lerner Research Institute, Cleveland ClinicWilliam Harvey Research Institute, Clinical Pharmacology, Queen Mary University of LondonThe spatial and frontal QRS-T angles are electrocardiographic (ECG) predictors for arrhythmia. This work used genetic analyses to identify associated loci and pathways, and explore their relationships with other ECG traits and cardiovascular disease.https://doi.org/10.1038/s41467-023-36997-w
spellingShingle William J. Young
Jeffrey Haessler
Jan-Walter Benjamins
Linda Repetto
Jie Yao
Aaron Isaacs
Andrew R. Harper
Julia Ramirez
Sophie Garnier
Stefan van Duijvenboden
Antoine R. Baldassari
Maria Pina Concas
ThuyVy Duong
Luisa Foco
Jonas L. Isaksen
Hao Mei
Raymond Noordam
Casia Nursyifa
Anne Richmond
Meddly L. Santolalla
Colleen M. Sitlani
Negin Soroush
Sébastien Thériault
Stella Trompet
Stefanie Aeschbacher
Fariba Ahmadizar
Alvaro Alonso
Jennifer A. Brody
Archie Campbell
Adolfo Correa
Dawood Darbar
Antonio De Luca
Jean-François Deleuze
Christina Ellervik
Christian Fuchsberger
Anuj Goel
Christopher Grace
Xiuqing Guo
Torben Hansen
Susan R. Heckbert
Rebecca D. Jackson
Jan A. Kors
Maria Fernanda Lima-Costa
Allan Linneberg
Peter W. Macfarlane
Alanna C. Morrison
Pau Navarro
David J. Porteous
Peter P. Pramstaller
Alexander P. Reiner
Lorenz Risch
Ulrich Schotten
Xia Shen
Gianfranco Sinagra
Elsayed Z. Soliman
Monika Stoll
Eduardo Tarazona-Santos
Andrew Tinker
Katerina Trajanoska
Eric Villard
Helen R. Warren
Eric A. Whitsel
Kerri L. Wiggins
Dan E. Arking
Christy L. Avery
David Conen
Giorgia Girotto
Niels Grarup
Caroline Hayward
J.Wouter Jukema
Dennis O. Mook-Kanamori
Morten Salling Olesen
Sandosh Padmanabhan
Bruce M. Psaty
Cristian Pattaro
Antonio Luiz P. Ribeiro
Jerome I. Rotter
Bruno H. Stricker
Pim van der Harst
Cornelia M. van Duijn
Niek Verweij
James G. Wilson
Michele Orini
Philippe Charron
Hugh Watkins
Charles Kooperberg
Henry J. Lin
James F. Wilson
Jørgen K. Kanters
Nona Sotoodehnia
Borbala Mifsud
Pier D. Lambiase
Larisa G. Tereshchenko
Patricia B. Munroe
Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease
Nature Communications
title Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease
title_full Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease
title_fullStr Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease
title_full_unstemmed Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease
title_short Genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease
title_sort genetic architecture of spatial electrical biomarkers for cardiac arrhythmia and relationship with cardiovascular disease
url https://doi.org/10.1038/s41467-023-36997-w
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AT cristianpattaro geneticarchitectureofspatialelectricalbiomarkersforcardiacarrhythmiaandrelationshipwithcardiovasculardisease
AT antonioluizpribeiro geneticarchitectureofspatialelectricalbiomarkersforcardiacarrhythmiaandrelationshipwithcardiovasculardisease
AT jeromeirotter geneticarchitectureofspatialelectricalbiomarkersforcardiacarrhythmiaandrelationshipwithcardiovasculardisease
AT brunohstricker geneticarchitectureofspatialelectricalbiomarkersforcardiacarrhythmiaandrelationshipwithcardiovasculardisease
AT pimvanderharst geneticarchitectureofspatialelectricalbiomarkersforcardiacarrhythmiaandrelationshipwithcardiovasculardisease
AT corneliamvanduijn geneticarchitectureofspatialelectricalbiomarkersforcardiacarrhythmiaandrelationshipwithcardiovasculardisease
AT niekverweij geneticarchitectureofspatialelectricalbiomarkersforcardiacarrhythmiaandrelationshipwithcardiovasculardisease
AT jamesgwilson geneticarchitectureofspatialelectricalbiomarkersforcardiacarrhythmiaandrelationshipwithcardiovasculardisease
AT micheleorini geneticarchitectureofspatialelectricalbiomarkersforcardiacarrhythmiaandrelationshipwithcardiovasculardisease
AT philippecharron geneticarchitectureofspatialelectricalbiomarkersforcardiacarrhythmiaandrelationshipwithcardiovasculardisease
AT hughwatkins geneticarchitectureofspatialelectricalbiomarkersforcardiacarrhythmiaandrelationshipwithcardiovasculardisease
AT charleskooperberg geneticarchitectureofspatialelectricalbiomarkersforcardiacarrhythmiaandrelationshipwithcardiovasculardisease
AT henryjlin geneticarchitectureofspatialelectricalbiomarkersforcardiacarrhythmiaandrelationshipwithcardiovasculardisease
AT jamesfwilson geneticarchitectureofspatialelectricalbiomarkersforcardiacarrhythmiaandrelationshipwithcardiovasculardisease
AT jørgenkkanters geneticarchitectureofspatialelectricalbiomarkersforcardiacarrhythmiaandrelationshipwithcardiovasculardisease
AT nonasotoodehnia geneticarchitectureofspatialelectricalbiomarkersforcardiacarrhythmiaandrelationshipwithcardiovasculardisease
AT borbalamifsud geneticarchitectureofspatialelectricalbiomarkersforcardiacarrhythmiaandrelationshipwithcardiovasculardisease
AT pierdlambiase geneticarchitectureofspatialelectricalbiomarkersforcardiacarrhythmiaandrelationshipwithcardiovasculardisease
AT larisagtereshchenko geneticarchitectureofspatialelectricalbiomarkersforcardiacarrhythmiaandrelationshipwithcardiovasculardisease
AT patriciabmunroe geneticarchitectureofspatialelectricalbiomarkersforcardiacarrhythmiaandrelationshipwithcardiovasculardisease