ArticleHuman molecular genetics2016
Twenty-eight genetic loci associated with ST-T-wave amplitudes of the electrocardiogram.
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Article in Human molecular genetics, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 2 of them syntheses that pooled it.
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15citing papers in PubMed, 2 pooled it
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Who cites it
15 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- KCND3 potassium channel gene variant confers susceptibility to electrocardiographic early repolarization pattern.JCI insight · 2019Pooled it
- Genome-wide association meta-analysis of 30,000 samples identifies seven novel loci for quantitative ECG traits.European journal of human genetics : EJHG · 2019Pooled it
- Genetic analyses across cardiovascular traits: leveraging genetic correlations to empower locus discovery and prediction in common cardiovascular diseases.NPJ genomic medicine · 2025Article
- Genome-Wide Association Study for Resting Electrocardiogram in the Qatari Population Identifies 6 Novel Genes and Validates Novel Polygenic Risk Scores.Journal of the American Heart Association · 2025Article
- Exploring the impact of electrocardiographic parameters on the risk of common arrhythmias: a two-sample Mendelian randomization study.Journal of thoracic disease · 2024Article
- Genome-wide association studies of cardiac electrical phenotypes.Cardiovascular research · 2020Review
- Tissue-Specific Requirement for the GINS Complex During Zebrafish Development.Frontiers in cell and developmental biology · 2020Article
- Functional characterization of SCN10A variants in several cases of sudden unexplained death.Forensic science international · 2019Article
- Integrative Functional Annotation of 52 Genetic Loci Influencing Myocardial Mass Identifies Candidate Regulatory Variants and Target Genes.Circulation. Genomic and precision medicine · 2019Article
- Genomic approaches for the elucidation of genes and gene networks underlying cardiovascular traits.Biophysical reviews · 2018Review
- Nitric oxide signalling in cardiovascular health and disease.Nature reviews. Cardiology · 2018Review
- NKX2-5 regulates human cardiomyogenesis via a HEY2 dependent transcriptional network.Nature communications · 2018Article
- Genetic study links components of the autonomous nervous system to heart-rate profile during exercise.Nature communications · 2018Article
- Brugada Syndrome-Associated Genetic Loci Are Associated With J-Point Elevation and an Increased Risk of Cardiac Arrest.Frontiers in physiology · 2018Article
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Authors and funding
30 authors.
Niek VerweijDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, 301 Binney Street, Cambridge, MA 02142, USA Cardiovascular Research Center and Center for Human Genetic Research, Massachusetts General Hospital, Boston, Massachusetts, The Netherlands.
Irene Mateo LeachDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Aaron IsaacsDepartment of Epidemiology, Genetic Epidemiology Unit, Rotterdam, The Netherlands CARIM School of Cardiovascular Diseases, Maastricht Centre for Systems Biology (MaCSBio), and Department of Biochemistry, Maastricht University, Maastricht, The Netherlands.
Dan E ArkingMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Joshua C BisDepartment of Medicine, Cardiovascular Health Research Unit, Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.
Tune H PersDivision of Endocrinology, Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, USA Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, 301 Binney Street, Cambridge, MA 02142, USA.
Marten E Van Den BergDepartment of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands.
Leo-Pekka LyytikäinenDepartment of Clinical Chemistry, Fimlab Laboratories and University of Tampere School of Medicine, Tampere 33520, Finland.
Phil BarnettDepartment of Anatomy, Embryology and Physiology, Academic Medical Center, University of Amsterdam, 1105 AZ Amsterdam, The Netherlands.
Xinchen WangDepartment of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
LifeLines Cohort Study
Elsayed Z SolimanDivision of Public Health Sciences, Epidemiological Cardiology Research Center (EPICARE), Wake Forest School of Medicine, Winston Salem, NC, USA.
Cornelia M Van DuijnDepartment of Epidemiology, Genetic Epidemiology Unit, Rotterdam, The Netherlands.
Mika KähönenDepartment of Clinical Physiology, Tampere University Hospital and University of Tampere School of Medicine, Tampere 33521, Finland.
Dirk J Van VeldhuisenDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Jan A KorsDepartment of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands.
Olli T RaitakariDepartment of Clinical Physiology and Nuclear Medicine, Turku University Hospital, Turku 20520, Finland Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Turku 20520, Finland.
Claudia T SilvaDepartment of Epidemiology, Genetic Epidemiology Unit, Rotterdam, The Netherlands.
Terho LehtimäkiDepartment of Clinical Chemistry, Fimlab Laboratories and University of Tampere School of Medicine, Tampere 33520, Finland.
Hans L HillegeDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands Trial Coordination Center, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Joel N HirschhornDivision of Endocrinology, Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, USA Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, 301 Binney Street, Cambridge, MA 02142, USA Department of Genetics, Harvard Medical School, Boston, USA.
Laurie A BoyerDepartment of Biology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
Wiek H Van GilstDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Alvaro AlonsoDivision of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, MN, USA.
Nona SotoodehniaDivision of Cardiology, Department of Medicine, Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA Department of Medicine, Cardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.
Mark EijgelsheimDepartment of Medical Informatics, Erasmus University Medical Center, Rotterdam, The Netherlands.
Rudolf A De BoerDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Paul I W De BakkerProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, 301 Binney Street, Cambridge, MA 02142, USA Department of Medical Genetics, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG Utrecht, The Netherlands.
Lude FrankeDepartment of Genetics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands.
Pim Van Der HarstDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands Department of Genetics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands Durrer Center for Cardiogenetic Research, ICIN-Netherlands Heart Institute, 3511 GC Utrecht, The Netherlands p.van.der.harst@umcg.nl.
Funding
Institute for Clinical and Translational Research (UL1)UL1RR025005 · NCRR · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2007 to 2011
$75.8MTransgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PETER J TONTONOZ · 2003 to 2026
$40.4MGenome-Wide Association Analysis in Essential Hypertension (FEHGAS study)R01HL086694 · NHLBI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ARAVINDA CHAKRAVARTI · 2007 to 2026
$21.2MCell Interactions in the Inflamed Intestinal MucosaR01DK075787 · NIDDK · BOSTON CHILDREN'S HOSPITAL · PI JOEL N HIRSCHHORN · 2007 to 2026
$13.1MEpidemiology of Venous Thrombosis & Pulmonary EmbolismR01HL059367 · NHLBI · UNIVERSITY OF MINNESOTA TWIN CITIES · PI TANG, WEIHONG · 1998 to 2024
$11.8MExceptional Survival: Trajectories to Functional Aging (CHS All Stars)R01AG023629 · NIA · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI NEWMAN, ANNE B. · 2004 to 2016
$9.5MCHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5MRare variants and NHLBI traits in deeply phenotyped cohortsR01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2014 to 2016
$8.9MCHS Events Follow-up StudyR01HL080295 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M · 2009 to 2014
$6.3MRare variants and NHLBI traits in deeply phenotyped cohortsU01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2017 to 2018
$5.6MProspective meta-analyses of drug-gene interactions: CHARGE GWAS consortiumR01HL103612 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M · 2011 to 2014
$5.4MWGA Study to Identify Genetic Variants Associated with CV Events in CHSR01HL087652 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M · 2007 to 2009
$5.1MNCRR NIH HHS UL1 RR025005NHGRI NIH HHS U01 HG004402NHLBI NIH HHS N01 HC055222NHLBI NIH HHS N01 HC085079NHLBI NIH HHS N01 HC085080NHLBI NIH HHS N01 HC085081NHLBI NIH HHS N01 HC085082NHLBI NIH HHS N01 HC085083NHLBI NIH HHS N01 HC085086NHLBI NIH HHS R01 HL059367NHLBI NIH HHS R01 HL080295NHLBI NIH HHS R01 HL086694NHLBI NIH HHS R01 HL087641NHLBI NIH HHS R01 HL087652NHLBI NIH HHS R01 HL103612NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL120393NHLBI NIH HHS U01 HL080295NHLBI NIH HHS U01 HL120393NIA NIH HHS R01 AG023629NIA NIH HHS R56 AG023629NIDDK NIH HHS P30 DK063491NIDDK NIH HHS R01 DK075787
Abstract
The ST-segment and adjacent T-wave (ST-T wave) amplitudes of the electrocardiogram are quantitative characteristics of cardiac repolarization. Repolarization abnormalities have been linked to ventricular arrhythmias and sudden cardiac death. We performed the first genome-wide association meta-analysis of ST-T-wave amplitudes in up to 37 977 individuals identifying 71 robust genotype-phenotype associations clustered within 28 independent loci. Fifty-four genes were prioritized as candidates underlying the phenotypes, including genes with established roles in the cardiac repolarization phase (SCN5A/SCN10A, KCND3, KCNB1, NOS1AP and HEY2) and others with as yet undefined cardiac function. These associations may provide insights in the spatiotemporal contribution of genetic variation influencing cardiac repolarization and provide novel leads for future functional follow-up.
Indexed as
ElectrocardiographyGenetic Predisposition to DiseaseGenome-Wide Association StudyAdaptor Proteins, Signal TransducingArrhythmias, CardiacBasic Helix-Loop-Helix ProteinsBrugada SyndromeCardiac Conduction System DiseaseDeath, Sudden, CardiacFemaleHeart Conduction SystemHumansMaleNAV1.5 Voltage-Gated Sodium ChannelPolymorphism, Single NucleotideRepressor ProteinsAdaptor Proteins, Signal TransducingBasic Helix-Loop-Helix ProteinsHEY2 protein, humanKCNB1 protein, humanKCND3 protein, humanNAV1.5 Voltage-Gated Sodium ChannelNOS1AP protein, humanRepressor ProteinsSCN5A protein, humanShab Potassium ChannelsShal Potassium Channels
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