SynthesisCirculation. Genomic and precision medicine2020
Genetic Determinants of Electrocardiographic P-Wave Duration and Relation to Atrial Fibrillation.
Open access · bronzeAbstract readMeta-Analysis
In one paragraph
Synthesis in Circulation. Genomic and precision medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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20citing papers in PubMed
2.7field-weighted citation impact, top 8% of its field
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Who cites it
20 citing papers in PubMed, 30 citations in OpenAlex.
- Atrial Cardiomyopathy: Pathophysiology, Diagnostic Approaches, and Prognostic Implications-A Narrative Review.Journal of clinical medicine · 2026Review
- CAND1 and CAND2 drive CUL4 substrate receptor exchange with largely comparable biochemical efficiency, unlike their relative effects on CUL1.Structure (London, England : 1993) · 2026Article
- Assessment of Autonomic Nervous System Function in Patients with Aortic Stenosis and Diabetes Mellitus.Diagnostics (Basel, Switzerland) · 2026Article
- Single-Nucleotide Polymorphisms,International journal of molecular sciences · 2025Review
- Polydactyly and syndactyly linked to GLI3 and TBX5 mutations: A pediatric case report.Global medical genetics · 2025Article
- Oxidative Stress Causes Mitochondrial and Electrophysiologic Dysfunction to Promote Atrial Fibrillation inCirculation. Arrhythmia and electrophysiology · 2025Article
- Molecular mechanisms of CAND2 in regulating SCF ubiquitin ligases.Nature communications · 2025Article
- Advancing drug development for atrial fibrillation by prioritising findings from human genetic association studies.EBioMedicine · 2024Article
- The Effect of Obesity on Repolarization and Other ECG Parameters.Journal of clinical medicine · 2024Article
- Exploring the Regulation and Function ofGenes · 2023Article
- Genetic Susceptibility to Atrial Fibrillation Identified via Deep Learning of 12-Lead Electrocardiograms.Circulation. Genomic and precision medicine · 2023Article
- Novel compound heterozygous variants in the RPL3L gene causing dilated cardiomyopathy type-2D: a case report and literature review.BMC medical genomics · 2023Review
- RPL3L-containing ribosomes determine translation elongation dynamics required for cardiac function.Nature communications · 2023Article
- Gene Polymorphism and Recurrent Atrial Fibrillation after Catheter Ablation: A Comprehensive Review.Reviews in cardiovascular medicine · 2023Review
- Global cognitive function correlates with P-wave dispersion in frail hypertensive older adults.Journal of clinical hypertension (Greenwich, Conn.) · 2022Article
- Roles of Cullin-RING Ubiquitin Ligases in Cardiovascular Diseases.Biomolecules · 2022Review
- Further Evidence of Autosomal Recessive Inheritance ofJournal of cardiovascular development and disease · 2022Article
- The Role of Patient-Specific Morphological Features of the Left Atrial Appendage on the Thromboembolic Risk Under Atrial Fibrillation.Frontiers in cardiovascular medicine · 2022Article
- Common variants in SCN10A gene associated with Brugada syndrome.Human molecular genetics · 2021Article
- Considerations for the Assessment of Substrates, Genetics and Risk Factors in Patients with Atrial Fibrillation.Arrhythmia & electrophysiology review · 2021Review
Corrections and comments
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Authors and funding
60 authors at 20 institutions in 7 countries.
Lu-Chen Weng *Cardiovascular Research Center (L.-C.W., A.W.H., P.L.H., P.T.E.), MGH, Boston.
Amelia Weber Hall *Cardiovascular Research Center (L.-C.W., A.W.H., P.L.H., P.T.E.), MGH, Boston.
Seung Hoan ChoiCardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA (L.-C.W., A.W.H., S.H.C., S.J.J., P.T.E., S.A.L.).
Sean J JurgensCardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA (L.-C.W., A.W.H., S.H.C., S.J.J., P.T.E., S.A.L.).
Jeffrey HaesslerFred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA (J.H., C.K.).
Nathan A BihlmeyerMcKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (N.A.B., D.E.A.).
Niels GrarupNovo Nordisk Foundation Center for Basic Metabolic Research (N.G., T.H.), Faculty of Health & Medicine Sciences, University of Copenhagen, Denmark.
Honghuang LinBoston University & NHLBI's Framingham Heart Study, Framingham, MA (H.L., J.K., E.J.B., K.L.L.).
Alexander TeumerDZHK (German Center for Cardiovascular Research), partner site Greifswald, Germany (A.T., U.V., M.D., S.B.F.).
Ruifang Li-GaoDepartment of Clinical Epidemiology (R.L.-G., D.O.M.-K.), Leiden University Medical Center, the Netherlands.
Jie YaoThe Institute for Translational Genomics & Population Sciences at Harbor-UCLA Medical Center, Torrance, CA (J.Y., X.G., K.D.T., H.J.L., J.I.R.).
Xiuqing GuoThe Institute for Translational Genomics & Population Sciences at Harbor-UCLA Medical Center, Torrance, CA (J.Y., X.G., K.D.T., H.J.L., J.I.R.).
Jennifer A BrodyCardiovascular Health Research Unit, Department of Medicine (J.A.B., N.S.), University of Washington.
Martina Müller-NurasyidChair of Genetic Epidemiology, IBE, Faculty of Medicine, LMU Munich, Germany (M.M.-N., K.S.).
Katharina SchrammChair of Genetic Epidemiology, IBE, Faculty of Medicine, LMU Munich, Germany (M.M.-N., K.S.).
Niek VerweijGenomics plc, Oxford, United Kingdom (N.V.).
Marten E van den BergDepartment of Epidemiology (M.E.v.d.B.).
Jessica van SettenErasmus MC, Medical Center Rotterdam, Division of Heart & Lungs, Department of Cardiology, University of Utrecht, University Medical Center Utrecht (J.v.S., F.W.A.).
Aaron IsaacsCARIM School for Cardiovascular Diseases (A.I.), Maastricht University, the Netherlands.
Julia RamírezNational Institute for Health Research, Barts Cardiovascular Biomedical Research Center (J.R., H.R.W., P.B.M.), Queen Mary University of London, London.
Helen R WarrenNational Institute for Health Research, Barts Cardiovascular Biomedical Research Center (J.R., H.R.W., P.B.M.), Queen Mary University of London, London.
Sandosh PadmanabhanInstitute of Cardiovascular & Medical Sciences, College of Medical, Veterinary & Life Sciences, University of Glasgow, United Kingdom (S.P.).
Jan A KorsDepartment of Medicine Informatics (J.A.K.), Erasmus University Medical Center, Rotterdam, the Netherlands.
Rudolf A de BoerDepartment of Cardiology (N.V., R.A.d.B., P.v.d.M., P.v.d.H.), University of Groningen & University Medical Center.
Peter van der MeerDepartment of Cardiology (N.V., R.A.d.B., P.v.d.M., P.v.d.H.), University of Groningen & University Medical Center.
Moritz F SinnerDepartment of Internal Medicine I (Cardiology), Hospital of the Ludwig-Maximilians-University (LMU) Munich, Germany (M.M.-N., K.S., M.F.S., S.K.).
Melanie WaldenbergerDZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance (M.F.S., M.W., S.K., A.P.).
Bruce M PsatyCardiovascular Health Research Unit, Departments of Medicine, Epidemiology & Health Services (B.M.P.), University of Washington.
Kent D TaylorThe Institute for Translational Genomics & Population Sciences at Harbor-UCLA Medical Center, Torrance, CA (J.Y., X.G., K.D.T., H.J.L., J.I.R.).
Uwe VölkerDZHK (German Center for Cardiovascular Research), partner site Greifswald, Germany (A.T., U.V., M.D., S.B.F.).
Jørgen K KantersLab of Experimental Cardiology (J.K.K.), Faculty of Health & Medicine Sciences, University of Copenhagen, Denmark.
Man LiDivision of Nephrology & Hypertension, Department of Internal Medicine, University of Utah School of Medicine, Salt Lake City, UT (M.L.).
Alvaro AlonsoDepartment of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA (A.A.).
Marco V PerezDepartment of Medicine, Stanford University, Palo Alto, CA (M.V.P.).
Ilonca VaartjesJulius Center for Health Sciences & Primary Care, University Medical Center Utrecht, Utrecht University, the Netherlands (I.V., M.L.B.).
Michiel L BotsJulius Center for Health Sciences & Primary Care, University Medical Center Utrecht, Utrecht University, the Netherlands (I.V., M.L.B.).
Paul L HuangCardiovascular Research Center (L.-C.W., A.W.H., P.L.H., P.T.E.), MGH, Boston.
Susan R HeckbertCardiovascular Health Research Unit, Department of Epidemiology (S.R.H.), University of Washington.
Henry J LinThe Institute for Translational Genomics & Population Sciences at Harbor-UCLA Medical Center, Torrance, CA (J.Y., X.G., K.D.T., H.J.L., J.I.R.).
Jelena KornejBoston University & NHLBI's Framingham Heart Study, Framingham, MA (H.L., J.K., E.J.B., K.L.L.).
Patricia B MunroeNational Institute for Health Research, Barts Cardiovascular Biomedical Research Center (J.R., H.R.W., P.B.M.), Queen Mary University of London, London.
Cornelia M van DuijnDepartment of Epidemiology (C.M.v.D.), Erasmus University Medical Center, Rotterdam, the Netherlands.
Folkert W AsselbergsErasmus MC, Medical Center Rotterdam, Division of Heart & Lungs, Department of Cardiology, University of Utrecht, University Medical Center Utrecht (J.v.S., F.W.A.).
Bruno H StrickerDepartment of Internal Medicine (B.H.S.).
Pim van der HarstDepartment of Cardiology (N.V., R.A.d.B., P.v.d.M., P.v.d.H.), University of Groningen & University Medical Center.
Stefan KääbDepartment of Internal Medicine I (Cardiology), Hospital of the Ludwig-Maximilians-University (LMU) Munich, Germany (M.M.-N., K.S., M.F.S., S.K.).
Annette PetersDZHK (German Center for Cardiovascular Research), partner site Munich Heart Alliance (M.F.S., M.W., S.K., A.P.).
Nona SotoodehniaCardiovascular Health Research Unit, Department of Medicine (J.A.B., N.S.), University of Washington.
Jerome I RotterThe Institute for Translational Genomics & Population Sciences at Harbor-UCLA Medical Center, Torrance, CA (J.Y., X.G., K.D.T., H.J.L., J.I.R.).
Dennis O Mook-KanamoriDepartment of Clinical Epidemiology (R.L.-G., D.O.M.-K.), Leiden University Medical Center, the Netherlands.
Marcus DörrDZHK (German Center for Cardiovascular Research), partner site Greifswald, Germany (A.T., U.V., M.D., S.B.F.).
Stephan B FelixDZHK (German Center for Cardiovascular Research), partner site Greifswald, Germany (A.T., U.V., M.D., S.B.F.).
Allan LinnebergDepartment of Clinical Medicine (A.L.), Faculty of Health & Medicine Sciences, University of Copenhagen, Denmark.
Torben HansenNovo Nordisk Foundation Center for Basic Metabolic Research (N.G., T.H.), Faculty of Health & Medicine Sciences, University of Copenhagen, Denmark.
Dan E ArkingMcKusick-Nathans Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD (N.A.B., D.E.A.).
Charles KooperbergFred Hutchinson Cancer Research Center, Division of Public Health Sciences, Seattle, WA (J.H., C.K.).
Emelia J BenjaminBoston University & NHLBI's Framingham Heart Study, Framingham, MA (H.L., J.K., E.J.B., K.L.L.).
Kathryn L LunettaBoston University & NHLBI's Framingham Heart Study, Framingham, MA (H.L., J.K., E.J.B., K.L.L.).
Patrick T EllinorCardiovascular Research Center (L.-C.W., A.W.H., P.L.H., P.T.E.), MGH, Boston.
Steven A LubitzCardiac Arrhythmia Service (P.T.E, S.A.L.), MGH, Boston.
Broad Institute · USBoston University · USErasmus MC · NLHelmholtz Zentrum München · DEUniversitätsmedizin Greifswald · DEUniversity Medical Center Groningen · NLQueen Mary University of London · GBUniversity of California, Los Angeles · USCape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa · ZAGerman Centre for Cardiovascular Research · DEJohns Hopkins University · USLeiden University Medical Center · NLNovo Nordisk Foundation · DKUniversity Medical Center Utrecht · NLUniversity of Copenhagen · DKDutch Health Care Inspectorate · NLEmory University · USFordham University · USFramingham Heart Study · USHoughton Mifflin Harcourt (United States) · US
Funding
FRAMINGHAM HEART STUDY - YEAR 5 EXAM75N92019D00031 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · 2019 to 2024
$29.8MIDENTIFICATION OF COMMON GENETIC VARIANTS FOR ATRIAL FIBRILLATION AND PR INTERVALR01HL092577 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI BENJAMIN, EMELIA J., ELLINOR, PATRICK THOMAS · 2009 to 2025
$20.6MPredoctoral Training Program in Human GeneticsT32GM007814 · NIGMS · JOHNS HOPKINS UNIVERSITY · PI VALLE, DAVID · 1985 to 2021
$10.6MCHARGE 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 research resources for the cardiovascular health of older adultsU01HL130114 · NHLBI · UNIVERSITY OF WASHINGTON · PI BURKE, GREGORY L, KRONMAL, RICHARD A · 2016 to 2019
$6.6MRare variants and NHLBI traits in deeply phenotyped cohortsU01HL120393 · NHLBI · UNIVERSITY OF WASHINGTON · PI PSATY, BRUCE M, RICE, KENNETH M. · 2017 to 2018
$5.6MGenomics of Cardiac ArrhythmiasR01HL139731 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI ELLINOR, PATRICK THOMAS · 2018 to 2022
$3.3MAFGen Consortium: Atrial Fibrillation Genomics to Functional AnalysesR01HL128914 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI BENJAMIN, EMELIA J., ELLINOR, PATRICK THOMAS · 2015 to 2018
$3.1MGenomics of Cardiac Electrical Activity and ArrhythmiaR01HL116747 · NHLBI · UNIVERSITY OF WASHINGTON · PI ARKING, DAN E, SOTOODEHNIA, NONA · 2013 to 2016
$2.8MGenomics of Sudden Cardiac Arrest Among African AmericansR01HL111089 · NHLBI · UNIVERSITY OF WASHINGTON · PI SOTOODEHNIA, NONA · 2012 to 2015
$2.6MMentoring in Arrhythmia ResearchK24HL105780 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI ELLINOR, PATRICK THOMAS · 2011 to 2020
$1.2MAmerican Heart Association-American Stroke Association 16EIA26410001American Heart Association-American Stroke Association 18SFRN34250007Medical Research Council MR/N025083/1NHLBI NIH HHS 75N92019D00031NHLBI NIH HHS K24 HL105780NHLBI NIH HHS K24 HL148521NHLBI NIH HHS R01 HL092577NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL111089NHLBI NIH HHS R01 HL116747NHLBI NIH HHS R01 HL120393NHLBI NIH HHS R01 HL128914NHLBI NIH HHS R01 HL139731NHLBI NIH HHS R01 HL141989NHLBI NIH HHS U01 HL120393NHLBI NIH HHS U01 HL130114NIGMS NIH HHS T32 GM007814
Abstract
backgroundThe P-wave duration (PWD) is an electrocardiographic measurement that represents cardiac conduction in the atria. Shortened or prolonged PWD is associated with atrial fibrillation (AF). We used exome-chip data to examine the associations between common and rare variants with PWD.
methodsFifteen studies comprising 64 440 individuals (56 943 European, 5681 African, 1186 Hispanic, 630 Asian) and ≈230 000 variants were used to examine associations with maximum PWD across the 12-lead ECG. Meta-analyses summarized association results for common variants; gene-based burden and sequence kernel association tests examined low-frequency variant-PWD associations. Additionally, we examined the associations between PWD loci and AF using previous AF genome-wide association studies.
resultsWe identified 21 common and low-frequency genetic loci (14 novel) associated with maximum PWD, including several AF loci (
conclusionsOur results highlight multiple novel genetic loci associated with PWD, and underscore the shared mechanisms of atrial conduction and AF. Prolonged PWD may be an endophenotype for several different genetic mechanisms of AF.
Indexed as
ElectrocardiographyAtrial FibrillationCardiac MyosinsConnectinGenetic VariationGenome-Wide Association StudyHomeobox Protein PITX2Homeodomain ProteinsHumansMyosin Heavy ChainsNAV1.8 Voltage-Gated Sodium ChannelQuantitative Trait LociTranscription FactorsCardiac MyosinsConnectinHomeobox Protein PITX2Homeodomain ProteinsMYH6 protein, humanMyosin Heavy ChainsNAV1.8 Voltage-Gated Sodium ChannelSCN10A protein, humanTranscription FactorsTTN protein, humanatrial fibrillationelectrophysiologyexomegeneticgenome-wide association studiespopulation
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