ArticleNature genetics2025
The impact of common and rare genetic variants on bradyarrhythmia development.
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Article in Nature genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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15citing papers in PubMed, 1 pooled it
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Genetic insights into cardiac conduction disorders from genome-wide association studies.Human genomics · 2025Pooled it
- Meta-Analysis of Genome-Wide Association Studies of Doxorubicin-Induced Arrhythmia IdentifiesCirculation. Genomic and precision medicine · 2026Article
- Integrating multi-ancestry common and rare variant mapping accelerates therapeutic target discovery.medRxiv : the preprint server for health sciences · 2026Article
- Integrated precise temperature regulation and electrophysiology sensing system for nanoplasmonic photothermal cardiac bradyarrhythmia therapy.Microsystems & nanoengineering · 2026Article
- Prioritizing Discovery and Advancements in Arrhythmia Therapies: NIH/NHLBI Workshop.JACC. Clinical electrophysiology · 2026Review
- Gene-gene interactions between a LMNA variant and common polymorphisms drive early-onset atrial fibrillation.Nature communications · 2026Article
- Rare coding variant architecture and gene discovery from 130,000 sequenced cases of atrial fibrillation.Research square · 2026Article
- The cardiac conduction system: development, function and therapeutic targets.Nature reviews. Cardiology · 2026Review
- Bradycardia in Athletes: Prevalence, Mechanisms, and Risks.Circulation · 2026Article
- Genomic Structural Equation Modeling Combined With Post-GWAS Analysis Identifies Two Risk Gene Loci and Functionally Sensitive Genes Associated With Cardiac Conduction Block.Genetics research · 2026Article
- Meta-analysis of genome-wide association studies of doxorubicin-induced arrhythmia identifiesmedRxiv : the preprint server for health sciences · 2025Article
- Article
- PITX2 dosage-dependent changes in pacemaker cell state underlie sinus node dysfunction and atrial arrhythmias.Nature communications · 2025Article
- Towards improved fine-mapping of candidate causal variants.Nature reviews. Genetics · 2025Review
- CCDC141 is a Connectin/Titin and Nesprin-1 binding protein that adapts cardiomyocytes to mechanical stress.Communications biology · 2025Article
Corrections and comments
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Authors and funding
66 authors.
Lu-Chen Weng *Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.ORCID 0000-0003-1475-4930
Joel T Rämö *Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland.ORCID 0000-0002-6429-5149
Sean J Jurgens *Cardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-1605-9782
Shaan Khurshid *Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
Mark ChaffinCardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-1234-5562
Amelia Weber HallGene Regulation Observatory, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-7915-0313
Valerie N MorrillCardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Xin WangCardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-0322-8970
Victor NauffalCardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Yan V SunVA Atlanta Healthcare System, Decatur, GA, USA.ORCID 0000-0002-2838-1824
Dominik BeerHeart Institute, Geisinger, Danville, PA, USA.
Simon LeeIcahn School of Medicine at Mount Sinai, New York City, NY, USA.
Girish N NadkarniIcahn School of Medicine at Mount Sinai, New York City, NY, USA.ORCID 0000-0001-6319-4314
ThuyVy DuongMcKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Biqi WangDepartment of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.
Tomasz CzubaThe Wallenberg Laboratory/Department of Molecular and Clinical Medicine, Institute of Medicine, Gothenburg University, Gothenburg, Sweden.
Thomas R AustinCardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.
Zachary T YonedaDepartment of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Daniel J FriedmanDivision of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
Anne ClaytonIntermountain Heart Institute, Intermountain Medical Center, Murray, UT, USA.
Matthew C HymanDivision of Cardiac Electrophysiology, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-4050-6925
Renae L JudyDepartment of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Allan C SkanesSection of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, Western University, London, Ontario, Canada.
Kate M OrlandDepartment of Medicine, Division of Cardiovascular Medicine, University of Wisconsin-Madison, Madison, WI, USA.
Timothy M TreuVA Boston Healthcare System, Boston, MA, USA.
Matthew T OetjensAutism and Developmental Medicine Institute, Geisinger, Lewisburg, PA, USA.ORCID 0000-0003-0955-9356
Alvaro AlonsoDepartment of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.ORCID 0000-0002-2225-8323
Elsayed Z SolimanEpidemiological Cardiology Research Center, Section on Cardiovascular Medicine, Department of Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.ORCID 0000-0001-5632-8150
Honghuang LinDepartment of Medicine, University of Massachusetts Chan Medical School, Worcester, MA, USA.ORCID 0000-0003-3043-3942
Kathryn L LunettaDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.ORCID 0000-0002-9268-810X
Jesper van der PalsDepartment of Cardiology, Clinical Sciences, Lund University and Skane University Hospital, Lund, Sweden.
Tariq Z IssaFeinberg School of Medicine, Northwestern University, Chicago, IL, USA.
Navid A NafissiDivision of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA.ORCID 0000-0003-0706-9548
Heidi T MayIntermountain Heart Institute, Intermountain Medical Center, Murray, UT, USA.
Peter Leong-SitSection of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, Western University, London, Ontario, Canada.
Carolina RoselliCardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0001-5267-6756
Seung Hoan ChoiCardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-2797-3190
FinnGen
Million Veteran Program
Regeneron Genetics Center
Habib R KhanSection of Cardiac Electrophysiology, Western University, London, Ontario, Canada.ORCID 0000-0002-4828-5768
Stacey KnightIntermountain Heart Institute, Intermountain Medical Center, Murray, UT, USA.ORCID 0000-0003-0092-7327
Richard Karlsson LinnérAutism and Developmental Medicine Institute, Geisinger, Lewisburg, PA, USA.
Connie R BezzinaDepartment of Experimental Cardiology, Amsterdam Cardiovascular Sciences, Heart Center, Amsterdam University Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.ORCID 0000-0002-0633-3514
Samuli RipattiInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.ORCID 0000-0002-0504-1202
Susan R HeckbertCardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.ORCID 0000-0002-7100-512X
J Michael GazianoVA Boston Healthcare System, Boston, MA, USA.
Ruth J F LoosCharles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York City, NY, USA.ORCID 0000-0002-8532-5087
Bruce M PsatyCardiovascular Health Research Unit, University of Washington, Seattle, WA, USA.
J Gustav SmithThe Wallenberg Laboratory/Department of Molecular and Clinical Medicine, Institute of Medicine, Gothenburg University, Gothenburg, Sweden.
Emelia J BenjaminDepartment of Medicine, Boston University Chobanian & Avedisian School of Medicine, Boston, MA, USA.ORCID 0000-0003-4076-2336
Dan E ArkingMcKusick-Nathans Institute, Department of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID 0000-0001-8980-8695
Daniel J RaderDepartments of Medicine and Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0002-9245-9876
Svati H ShahDivision of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
Dan M RodenVanderbilt University Medical Center, Nashville, TN, USA.ORCID 0000-0002-6302-0389
Scott M DamrauerDepartment of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID 0000-0001-8009-1632
Lee L EckhardtDepartment of Medicine, Division of Cardiovascular Medicine, University of Wisconsin-Madison, Madison, WI, USA.
Jason D RobertsSection of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, Western University, London, Ontario, Canada.
Michael J CutlerIntermountain Heart Institute, Intermountain Medical Center, Murray, UT, USA.ORCID 0000-0001-9498-7472
M Benjamin ShoemakerDepartment of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Christopher M HaggertyHeart Institute, Geisinger, Danville, PA, USA.
Kelly ChoVA Boston Healthcare System, Boston, MA, USA.
Aarno PalotieInstitute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science (HiLIFE), University of Helsinki, Helsinki, Finland.ORCID 0000-0002-2527-5874
Peter W F WilsonVA Atlanta Healthcare System, Decatur, GA, USA.
Patrick T EllinorCardiovascular Disease Initiative, The Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID 0000-0002-2067-0533
Steven A LubitzTelemachus and Irene Demoulas Family Foundation Center for Cardiac Arrhythmias, Massachusetts General Hospital, Boston, MA, USA. slubitz@mgh.harvard.edu.ORCID 0000-0002-9599-4866
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
$20.6MMULTIDISCIPLINARY HEART &VASCULAR DISEASEST32HL007101 · NHLBI · DUKE UNIVERSITY · PI FREEDMAN, NEIL J. · 1985 to 2020
$9.8MCHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5MGenomics of Cardiac ArrhythmiasR01HL139731 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI ELLINOR, PATRICK THOMAS · 2018 to 2022
$3.3MA Precision Medicine Approach to Arrhythmogenic CardiomyopathyR01HL141901 · NHLBI · GEISINGER CLINIC · PI CARRUTH, ERIC DAVID · 2019 to 2023
$3.1MUsing Electrocardiogram Genetics to Inform Arrhythmia RiskR01HL157635 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI ELLINOR, PATRICK THOMAS, MIRSHAHI, TOORAJ · 2022 to 2025
$2.9MAssessing Alzheimer disease risk and heterogeneity using multimodal machine learning approachesU01AG068221 · NIA · UNIV OF MASSACHUSETTS MED SCH WORCESTER · PI DESTEFANO, ANITA L, LIN, HONGHUANG · 2021 to 2024
$2.5MDeep Mutational Scanning and Functional Analysis of Repolarization DeterminantsR01HL163987 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI ECKHARDT, LEE LOCHBAUM · 2022 to 2025
$1.6MKCNJ2-Induced Arrhythmia Mechanisms in CPVT and Heart Failure.R01HL139738 · NHLBI · UNIVERSITY OF WISCONSIN-MADISON · PI ECKHARDT, LEE LOCHBAUM · 2018 to 2021
$1.5MElectrocardiogram-based deep learning and decision analysis to improve atrial fibrillation risk estimationK23HL169839 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI Shaan Khurshid · 2023 to 2026
$860kAmerican Heart Association (American Heart Association, Inc.) 18SFRN34110082American Heart Association (American Heart Association, Inc.) 18SFRN34230127American Heart Association (American Heart Association, Inc.) 18SFRN34250007American Heart Association (American Heart Association, Inc.) 23CDA1050571CSRD VA IK2 CX001780Fondation Leducq TNE FANTASY 19CV03Hartstichting (Dutch Heart Foundation) 03-007-2022-0035NHLBI NIH HHS 75N92019D00031NHLBI NIH HHS K23 HL169839NHLBI NIH HHS R01 HL092577NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL139731NHLBI NIH HHS R01 HL139738NHLBI NIH HHS R01 HL141901NHLBI NIH HHS R01 HL157635NHLBI NIH HHS R01 HL163987NHLBI NIH HHS T32 HL007101NIA NIH HHS U01 AG068221
Abstract
To broaden our understanding of bradyarrhythmias and conduction disease, we performed common variant genome-wide association analyses in up to 1.3 million individuals and rare variant burden testing in 460,000 individuals for sinus node dysfunction (SND), distal conduction disease (DCD) and pacemaker (PM) implantation. We identified 13, 31 and 21 common variant loci for SND, DCD and PM, respectively. Four well-known loci (SCN5A/SCN10A, CCDC141, TBX20 and CAMK2D) were shared for SND and DCD, while others were more specific for SND or DCD. SND and DCD showed a moderate genetic correlation (r
Indexed as
BradycardiaGenetic VariationCardiac Conduction System DiseaseFemaleGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansMaleNAV1.5 Voltage-Gated Sodium ChannelPacemaker, ArtificialPhenotypePolymorphism, Single NucleotideSick Sinus SyndromeNAV1.5 Voltage-Gated Sodium ChannelSCN5A protein, human
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