SynthesisNature genetics2025
Sequencing in over 50,000 cases identifies coding and structural variation underlying atrial fibrillation risk.
Abstract readMeta-Analysis
In one paragraph
Synthesis in Nature genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 2 of them syntheses that pooled it.
0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed, 2 pooled it
–field-weighted citation impact
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
22 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Freely available genomic datasets for atrial fibrillation research: current resources and analytical pipeline.Frontiers in genetics · 2026Pooled it
- Cross-population GWAS and proteomics improve risk prediction and reveal mechanisms in atrial fibrillation.Nature communications · 2025Pooled it
- Effects of SGLT2 inhibition on incident heart failure in carriers of cardiomyopathy-associated genetic variants.Nature medicine · 2026Trial
- Clinical Variability Including Non-Dilated Left Ventricular and Dilated Cardiomyopathy in a Pedigree With an Intragenic CTNNA3 Copy Number Variation.Clinical genetics · 2026Article
- The clinical pathophysiology of atrial fibrillation: outstanding questions from bedside to bench and back.Physiological reviews · 2026Review
- Chromatin topology control by a muscle-specific ribosomal protein.bioRxiv : the preprint server for biology · 2026Article
- Cardiovascular Genetic Epidemiology in the Genome-Wide Era: From Association Discovery to Mechanistic Dissection and Clinical Translation.Cardiovascular drugs and therapy · 2026Review
- The Biobank Rare Variant consortium powers the discovery of rare genetic associations through global collaboration.medRxiv : the preprint server for health sciences · 2026Article
- Uncovering Novel Atrial Fibrillation Genetics Through Pleiotropic Overlap with Life's Essential 8.Biomedicines · 2026Article
- 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
- Genetic evaluation of early-onset atrial fibrillation: impact on patient management.European heart journal · 2026Article
- Early differentiation between paroxysmal and persistent atrial fibrillation based on interpretable machine learning: a multicenter retrospective study.BioData mining · 2026Article
- Association of radiotherapy with atrial fibrillation-related gene expression in breast cancer patients: a study based on the TCGA-BRCA database.Discover oncology · 2026Article
- Unravelling the genetic architecture of cardiovascular disease through structural variant detection with whole-genome sequencing.Frontiers in genetics · 2026Review
- Transforming atrial fibrillation management by targeting comorbidities and reducing atrial fibrillation burden: the 10th AFNET/EHRA consensus conference.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2025Article
- TBX5 and CHD4 Coordinately Activate Atrial Cardiomyocyte Genes to Maintain Cardiac Rhythm Homeostasis.Circulation · 2025Article
- Genomic medicine for heart failure prediction in patients with atrial fibrillation.Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2025Article
- A cross-tissue transcriptome-wide association study identifies novel susceptibility genes for atrial fibrillation.Journal of arrhythmia · 2025Article
- Predicting Atrial Fibrillation After Stroke by Combining Polygenic Risk Scores and Clinical Features.Stroke · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
105 authors.
Seung Hoan Choi *Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-2797-3190
Sean J Jurgens *Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-1605-9782
Ling XiaoCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-5463-5576
Matthew C HillCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Christopher M HaggertyDepartment of Translational Data Science and Informatics, Geisinger, Danville, PA, USA.ORCID http://orcid.org/0000-0002-3227-4490
Garðar SveinbjörnssondeCODE genetics/Amgen, Reykjavik, Iceland.ORCID http://orcid.org/0000-0003-2429-9468
Valerie N MorrillCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Nicholas A MarstonTIMI Study Group, Boston, MA, USA.ORCID http://orcid.org/0000-0001-6164-4617
Lu-Chen WengCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-1475-4930
James P PirruccelloCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-6088-4037
David O ArnardeCODE genetics/Amgen, Reykjavik, Iceland.
Daniel Fannar GudbjartssondeCODE genetics/Amgen, Reykjavik, Iceland.
Helene MantineoCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Aenne S von FalkenhausenDepartment of Medicine I, University Hospital Munich, Ludwig Maximilian University, Munich, Germany.ORCID http://orcid.org/0000-0001-9453-3016
Andrea NataleTexas Cardiac Arrhythmia Institute, St David's Medical Center, Austin, TX, USA.
Arnljot TveitDepartment of Medical Research, Bærum Hospital, Vestre Viken Hospital Trust, Gjettum, Norway.
Bastiaan GeelhoedDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Carolina RoselliCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-5267-6756
David R Van WagonerDepartment of Cardiovascular & Metabolic Sciences, Cleveland Clinic, Cleveland, OH, USA.ORCID http://orcid.org/0000-0001-8250-9828
Dawood DarbarDivision of Cardiology, University of Illinois at Chicago, Chicago, IL, USA.ORCID http://orcid.org/0000-0002-4103-5977
Doreen HaaseAtrial Fibrillation NETwork (AFNET), Münster, Germany.
Elsayed Z SolimanEpidemiological Cardiology Research Center (EPICARE), Department of Internal Medicine, Cardiology Section, Wake Forest School of Medicine, Winston-Salem, NC, USA.ORCID http://orcid.org/0000-0001-5632-8150
Giovanni E DavogusttoDepartment of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Goo JunHuman Genetics Center, University of Texas Health Science Center at Houston, Houston, TX, USA.
Hugh CalkinsCardiac Arrhythmia Service, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Jeffrey L AndersonIntermountain Heart Institute, Intermountain Medical Center, Murray, UT, USA.
Jennifer A BrodyCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0001-8509-148X
Jennifer L HalfordCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-1454-3650
John BarnardDepartments of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, USA.ORCID http://orcid.org/0000-0003-2403-8268
John E HokansonDepartment of Epidemiology, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.
Jonathan D SmithDepartment of Cardiovascular & Metabolic Sciences, Cleveland Clinic, Cleveland, OH, USA.ORCID http://orcid.org/0000-0002-0415-386X
Joshua C BisCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-3409-1110
Kendra YoungDepartment of Epidemiology, University of Colorado, Anschutz Medical Campus, Aurora, CO, USA.ORCID http://orcid.org/0000-0002-8664-7635
Linda S B JohnsonDepartment of Clinical Physiology, Department of Clinical Sciences, Skåne University Hospital and Lund University, Lund, Sweden.ORCID http://orcid.org/0000-0002-2249-8220
Lorenz RischInstitute of Laboratory Medicine, Faculty of Medical Sciences, Private University of the Principality of Liechtenstein, Triesen, Liechtenstein.ORCID http://orcid.org/0000-0003-2692-6699
Lorne J GulaSection of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, Western University, London, Ontario, Canada.
Lydia Coulter KweeDuke Molecular Physiology Institute, Duke University School of Medicine, Durham, NC, USA.ORCID http://orcid.org/0000-0002-6997-8571
Mark D ChaffinCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-1234-5562
Michael KühneCardiology/Electrophysiology, University Hospital Basel, University of Basel, Basel, Switzerland.ORCID http://orcid.org/0000-0002-2937-3711
Michael PreussThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0001-5266-8465
Namrata GuptaProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Navid A NafissiDivision of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA.ORCID http://orcid.org/0000-0003-0706-9548
Nicholas L SmithDepartment of Epidemiology, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0003-3483-353X
Peter M NilssonDepartment of Clinical Sciences, Clinical Research Center, Lund University, Malmö, Sweden.ORCID http://orcid.org/0000-0002-5652-8459
Pim van der HarstDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.
Quinn S WellsDepartment of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Renae L JudyDepartment of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Renate B SchnabelAtrial Fibrillation NETwork (AFNET), Münster, Germany.ORCID http://orcid.org/0000-0001-7170-9509
Renee JohnsonMolecular Cardiology Division, Victor Chang Cardiac Research Institute, Sydney, New South Wales, Australia.
Roelof A J SmitThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0001-9822-6726
Stacey GabrielProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Stacey KnightIntermountain Heart Institute, Intermountain Medical Center, Murray, UT, USA.ORCID http://orcid.org/0000-0003-0092-7327
Tetsushi FurukawaDepartment of Bio-Informational Pharmacology, Medical Research Institute, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
Thomas W BlackwellCenter for Statistical Genetics, Department of Biostatistics, University of Michigan School of Public Health, Ann Arbor, MI, USA.
Victor NauffalCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0001-7199-299X
Xin WangCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-0322-8970
Yuan-I MinDepartment of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.ORCID http://orcid.org/0000-0003-2470-0004
Zachary T YonedaDepartment of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Zachary W M LaksmanDepartment of Medicine and the School of Biomedical Engineering, University of British Columbia, Vancouver, British Columbia, Canada.ORCID http://orcid.org/0000-0002-7790-541X
Connie R BezzinaDepartment of Experimental Cardiology, Heart Centre, Amsterdam Cardiovascular Sciences (Heart Failure & Arrhythmias), Amsterdam UMC, Amsterdam, The Netherlands.ORCID http://orcid.org/0000-0002-0633-3514
Alvaro AlonsoDepartment of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.ORCID http://orcid.org/0000-0002-2225-8323
Bruce M PsatyCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-7278-2190
Christine M AlbertDepartment of Cardiology, Smidt Heart Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0002-2081-1121
Dan E ArkingMcKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.ORCID http://orcid.org/0000-0001-8980-8695
Dan M RodenDepartments of Medicine, Pharmacology, and Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA.ORCID http://orcid.org/0000-0002-6302-0389
Daniel I ChasmanProgram in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0003-3357-0862
Daniel J RaderDepartment of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-9245-9876
David ConenPopulation Health Research Institute, McMaster University, Hamilton, Ontario, Canada.
David D McManusUniversity of Massachusetts Chan Medical School Worcester, Worcester, MA, USA.
Diane FatkinMolecular Cardiology Division, Victor Chang Cardiac Research Institute, Sydney, New South Wales, Australia.ORCID http://orcid.org/0000-0002-9010-9856
Emelia J BenjaminNHLBI and Boston University's Framingham Heart Study, Framingham, MA, USA.ORCID http://orcid.org/0000-0003-4076-2336
Eric BoerwinkleHuman 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.
Gregory M MarcusDivision of Cardiology, University of California, San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-5197-7696
Ingrid E ChristophersenDepartment of Medical Research, Bærum Hospital, Vestre Viken Hospital Trust, Gjettum, Norway.
J Gustav SmithDepartment of Cardiology, Lund University Diabetes Center and Wallenberg Center for Molecular Medicine, Clinical Sciences, Lund University and Skåne University Hospital, Lund, Sweden.
Jason D RobertsSection of Cardiac Electrophysiology, Division of Cardiology, Department of Medicine, Western University, London, Ontario, Canada.
Laura M RaffieldDepartment of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
M Benjamin ShoemakerDepartment of Medicine, Division of Cardiovascular Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
Michael H ChoChanning Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Michael J CutlerIntermountain Heart Institute, Intermountain Medical Center, Murray, UT, USA.ORCID http://orcid.org/0000-0001-9498-7472
Michiel RienstraDepartment of Cardiology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands.ORCID http://orcid.org/0000-0002-2581-070X
Mina K ChungDepartment of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, USA.
Morten S OlesenLaboratory for Molecular Cardiology, Department of Cardiology, Centre for Cardiac, Vascular, Pulmonary and Infectious Diseases, Copenhagen University Hospital Rigshospitalet, Copenhagen, Denmark.ORCID http://orcid.org/0000-0001-9477-5322
Moritz F SinnerDepartment of Medicine I, University Hospital Munich, Ludwig Maximilian University, Munich, Germany.ORCID http://orcid.org/0000-0002-6660-796X
Nona SotoodehniaCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, WA, USA.
Paulus KirchhofAtrial Fibrillation NETwork (AFNET), Münster, Germany.ORCID http://orcid.org/0000-0002-1881-0197
Ruth J F LoosThe Charles Bronfman Institute for Personalized Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0002-8532-5087
Saman NazarianDivision of Cardiovascular Medicine, Hospital of the University of Pennsylvania, Philadelphia, PA, USA.
Sanghamitra MohantyTexas Cardiac Arrhythmia Institute, St David's Medical Center, Austin, TX, USA.ORCID http://orcid.org/0000-0001-6601-944X
Scott M DamrauerDepartment of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0001-8009-1632
Stefan KaabDepartment of Medicine I, University Hospital Munich, Ludwig Maximilian University, Munich, Germany.ORCID http://orcid.org/0000-0001-8824-3581
Susan R HeckbertKaiser Permanente Washington Health Research Institute, Seattle, WA, USA.ORCID http://orcid.org/0000-0002-7100-512X
Susan RedlineDivision of Sleep and Circadian Disorders, Departments of Medicine and Neurology, Brigham and Women's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-6585-1610
Svati H ShahDivision of Cardiology, Department of Medicine, Duke University School of Medicine, Durham, NC, USA.
Toshihiro TanakaDepartment of Human Genetics and Disease Diversity, Tokyo Medical and Dental University (TMDU) Graduate School of Medical and Dental Sciences, Tokyo, Japan.ORCID http://orcid.org/0000-0001-6201-9784
Yusuke EbanaLife Science and Bioethics Research Center, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.ORCID http://orcid.org/0000-0002-5162-0838
Regeneron Genetics Center
NHLBI Trans-Omics for Precision Medicine (TOPMed) Consortium
Hilma HolmdeCODE genetics/Amgen, Reykjavik, Iceland.ORCID http://orcid.org/0000-0002-9517-6636
Kari StefanssondeCODE genetics/Amgen, Reykjavik, Iceland.ORCID http://orcid.org/0000-0003-1676-864X
Christian T RuffTIMI Study Group, Boston, MA, USA.
Marc S SabatineTIMI Study Group, Boston, MA, USA.
Kathryn L LunettaDepartment of Biostatistics, Boston University School of Public Health, Boston, MA, USA.ORCID http://orcid.org/0000-0002-9268-810X
Steven A LubitzCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA.ORCID http://orcid.org/0000-0002-9599-4866
Patrick T EllinorCardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA, USA. ellinor@mgh.harvard.edu.ORCID http://orcid.org/0000-0002-2067-0533
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
$20.6M(2 of 2) Genetic Epidemiology of COPDR01HL089856 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI SILVERMAN, EDWIN K · 2012 to 2016
$18.9MSingle Cell Analysis and ImmunogeneticsP01HL158505 · NHLBI · DANA-FARBER CANCER INST · PI Corey S Cutler · 2022 to 2026
$15.3MCHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5MPhenotypic and Molecular Signatures for Sleep Apnea and Related MorbiditiesR35HL135818 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI REDLINE, SUSAN S. · 2017 to 2023
$7.2MFunctional Genomics of Atrial Fibrillation in Human AtriaR01HL111314 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI BARNARD, JOHN, CHUNG, MINA KAY · 2012 to 2019
$6.1MSOLAR-Eclipse Computational Tools for Imaging GeneticsR01EB015611 · NIBIB · UNIVERSITY OF TEXAS HLTH SCI CTR HOUSTON · PI KOCHUNOV, PETER V. · 2012 to 2024
$5.0MLeveraging Family Data to Identify Genetic Variants for Sleep ApneaR01HL113338 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI LIN, XIHONG, REDLINE, SUSAN S. · 2012 to 2016
$4.4MProbing Phenotype-Genotype Relations After Whole Genome Sequencing in Patients with Atrial FibrillationR01HL155197 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI SHOEMAKER, MOORE BENJAMIN · 2021 to 2025
$4.1MGenetic and Functional Dissection of a Cluster of COPD GWAS Signals on Chromosome 4qR01HL147148 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI CHO, MICHAEL H., SILVERMAN, EDWIN K · 2019 to 2022
$3.5MThe VITAL Rhythm StudyR01HL116690 · NHLBI · BRIGHAM AND WOMEN'S HOSPITAL · PI ALBERT, CHRISTINE M · 2013 to 2020
$3.5MAmerican Heart Association (American Heart Association, Inc.) 18SFRN34110067American Heart Association (American Heart Association, Inc.) 18SFRN34110067.American 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.) 19SFRN34830063American Heart Association (American Heart Association, Inc.) 20CDA35260081American Heart Association (American Heart Association, Inc.) 961045American Heart Association (American Heart Association, Inc.) 9SFRN34830063American Heart Association-American Stroke Association 18SFRN34230127American Heart Association-American Stroke Association 19SFRN34830063British Heart Foundation (BHF) AA/18/2/34218British Heart Foundation (BHF) PG/17/30/32961British Heart Foundation (BHF) PG/20/22/35093CSRD VA IK2 CX001780Deutsche Forschungsgemeinschaft (German Research Foundation) Ki 731/4-1EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) 648131EC | EU Framework Programme for Research and Innovation H2020 | H2020 Priority Excellent Science | H2020 European Research Council (H2020 Excellent Science - European Research Council) 847770Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) 1R01HL128914Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) 1R01HL139731Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) 1R01HL164824-01Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) 1U01AG058589-01A1Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) 1U01AG068221-01A1Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) 2R01HL127564-05A1Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) HL-093613Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) HL113338Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) HL116690Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) HL43680Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) K08HL153950Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) K08HL159346Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) K24HL105780Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) P01HL158505Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) R01HL089856Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) R01HL092577Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) R01HL111024Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) R01HL111314Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) R01HL137927Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) R01HL141901Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) R01HL141989Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) R01HL147148Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) R01HL149352Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) R01HL155197Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) R01HL157635Foundation for the National Institutes of Health (Foundation for the National Institutes of Health, Inc.) R35HL135818Hartstichting (Dutch Heart Foundation) 03-007-2022-0035Hjärt-Lungfonden (Swedish Heart-Lung Foundation) 2019-0526MEXT | Japan Society for the Promotion of Science (JSPS) 17K07251MEXT | Japan Society for the Promotion of Science (JSPS) JP18H02804NHLBI NIH HHS 75N92019D00031NHLBI NIH HHS DP2 HL157540NHLBI NIH HHS K08 HL153950NHLBI NIH HHS K08 HL159346NHLBI NIH HHS K24 HL105780NHLBI NIH HHS P01 HL158505NHLBI NIH HHS R01 HL089856NHLBI NIH HHS R01 HL092577NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL111314NHLBI NIH HHS R01 HL113338NHLBI NIH HHS R01 HL116690NHLBI NIH HHS R01 HL128914NHLBI NIH HHS R01 HL137927NHLBI NIH HHS R01 HL138737NHLBI NIH HHS R01 HL139731NHLBI NIH HHS R01 HL141901NHLBI NIH HHS R01 HL141989NHLBI NIH HHS R01 HL147148NHLBI NIH HHS R01 HL155197NHLBI NIH HHS R01 HL157635NHLBI NIH HHS R01 HL167072NHLBI NIH HHS R01 HL172803NHLBI NIH HHS R21 HL093613NHLBI NIH HHS R35 HL135818NHLBI NIH HHS T32 HL139439NIA NIH HHS U01 AG068221NIBIB NIH HHS R01 EB015611NIH HHS S10 OD023696NIMH NIH HHS RF1 MH123163Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) 32003B_197524Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) 32473B_176178Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) 33CS30_148474Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (Swiss National Science Foundation) 33CS30_177520Stiftelsen för Strategisk Forskning (Swedish Foundation for Strategic Research) IRC15-0067Svenska Sällskapet för Medicinsk Forskning (Swedish Society for Medical Research) 2019-0354U.S. Department of Veterans Affairs (Department of Veterans Affairs) IK2-CX001780Vetenskapsrådet (Swedish Research Council) 2009-1039Vetenskapsrådet (Swedish Research Council) 2021-02273Vetenskapsrådet (Swedish Research Council) 349-2006-237
Abstract
Atrial fibrillation (AF) is a prevalent and morbid abnormality of the heart rhythm with a strong genetic component. Here, we meta-analyzed genome and exome sequencing data from 36 studies that included 52,416 AF cases and 277,762 controls. In burden tests of rare coding variation, we identified novel associations between AF and the genes MYBPC3, LMNA, PKP2, FAM189A2 and KDM5B. We further identified associations between AF and rare structural variants owing to deletions in CTNNA3 and duplications of GATA4. We broadly replicated our findings in independent samples from MyCode, deCODE and UK Biobank. Finally, we found that CRISPR knockout of KDM5B in stem-cell-derived atrial cardiomyocytes led to a shortening of the action potential duration and widespread transcriptomic dysregulation of genes relevant to atrial homeostasis and conduction. Our results highlight the contribution of rare coding and structural variants to AF, including genetic links between AF and cardiomyopathies, and expand our understanding of the rare variant architecture for this common arrhythmia.
Indexed as
Atrial FibrillationGenetic Predisposition to DiseaseCase-Control StudiesExome SequencingGenetic VariationGenome-Wide Association StudyHumansMyocytes, Cardiac
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