Evidence map›Paper›PMID 24486271›Full record

ArticleJournal of the American College of Cardiology2014

Novel genetic markers associate with atrial fibrillation risk in Europeans and Japanese.

Steven A Lubitz, Kathryn L Lunetta, Honghuang Lin, Dan E Arking, Stella Trompet, Guo Li, Bouwe P Krijthe, Daniel I Chasman, John Barnard, Marcus E Kleber and 52 more

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Journal of the American College of Cardiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 5 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
80citing papers in PubMed, 5 pooled it
13.8field-weighted citation impact, top 1% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

80 citing papers in PubMed, 5 syntheses or guidelines pooled it, 144 citations in OpenAlex.

  1. Pooled it
  2. 2017 HRS/EHRA/ECAS/APHRS/SOLAECE expert consensus statement on catheter and surgical ablation of 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 · 2018
    Guideline
  3. Pooled it
  4. Guideline
  5. 2012 HRS/EHRA/ECAS expert consensus statement on catheter and surgical ablation of atrial fibrillation: recommendations for patient selection, procedural techniques, patient management and follow-up, definitions, endpoints, and research trial design: a report of the Heart Rhythm Society (HRS) Task Force on Catheter and Surgical Ablation of Atrial Fibrillation. Developed in partnership with the European Heart Rhythm Association (EHRA), a registered branch of the European Society of Cardiology (ESC) and the European Cardiac Arrhythmia Society (ECAS); and in collaboration with the American College of Cardiology (ACC), American Heart Association (AHA), the Asia Pacific Heart Rhythm Society (APHRS), and the Society of Thoracic Surgeons (STS). Endorsed by the governing bodies of the American College of Cardiology Foundation, the American Heart Association, the European Cardiac Arrhythmia Society, the European Heart Rhythm Association, the Society of Thoracic Surgeons, the Asia Pacific Heart Rhythm Society, and the Heart Rhythm Society.Heart rhythm · 2012
    Guideline
  6. Trial
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Innovative approaches to atrial fibrillation prediction: should polygenic scores and machine learning be implemented in clinical practice?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 · 2024
    Review
  15. Review
  16. Genetics, transcriptomics, metagenomics, and metabolomics in the pathogenesis and prediction of atrial fibrillation.European heart journal supplements : journal of the European Society of Cardiology · 2024
    Article
  17. Article
  18. Review
  19. Genome and atrial fibrillation.Journal of arrhythmia · 2023
    Review
  20. Review

20 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

62 authors at 20 institutions in 9 countries.

Steven A Lubitz *Cardiac Arrhythmia Service, Massachusetts General Hospital, Boston, Massachusetts, USA.
Kathryn L Lunetta *Boston University and National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA.
Honghuang Lin *Boston University and National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA.
Dan E Arking *McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
Stella Trompet *Department of Cardiology, Leiden University Medical Center, Leiden, the Netherlands.
Guo Li *Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA.
Bouwe P Krijthe *Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Daniel I Chasman *Harvard Medical School, Boston, Massachusetts, USA.
John Barnard *Department of Quantitative Health Sciences, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Marcus E Kleber *Institute of Public Health, Social and Preventive Medicine, Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany.
Marcus Dörr *Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany.
Kouichi Ozaki *Laboratory for Cardiovascular Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Albert V Smith *Icelandic Heart Association, Kopavogur Iceland and University of Iceland Reykjavik, Iceland.
Martina Müller-Nurasyid *Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
Stefan Walter *Department of Society, Human Development & Health, Harvard School of Public Health, Boston, Massachusetts, USA.
Sunil K AgarwalWelch Center for Prevention, Epidemiology, and Clinical Research, Johns Hopkins University, Baltimore, Maryland, USA.
Joshua C BisCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA.
Jennifer A BrodyCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA.
Lin Y ChenCardiovascular Division, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
Brendan M EverettHarvard Medical School, Boston, Massachusetts, USA.
Ian FordRobertson Center for Biostatistics, University of Glasgow, United Kingdom.
Oscar H FrancoDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Tamara B HarrisLaboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
Albert HofmanDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Stefan KääbDepartment of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
Saagar MahidaLeeds General Infirmary, Great George Street, Leeds, UK.
Sekar KathiresanCenter for Human Genetic Research and Cardiovascular Research Center, Massachusetts General Hospital, Boston, Massachusetts, USA.
Michiaki KuboLaboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Lenore J LaunerLaboratory of Epidemiology and Population Sciences, Intramural Research Program, National Institute on Aging, National Institutes of Health, Bethesda, Maryland, USA.
Peter W MacFarlaneInstitute of Cardiovascular and Medical Sciences, University of Glasgow, United Kingdom.
Jared W MagnaniBoston University and National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA.
Barbara McKnightDepartment of Biostatistics, University of Washington, Seattle, Washington, USA.
David D McManusDepartments of Medicine and Quantitative Health Sciences, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Annette PetersDeutsches Forschungszentrum für Herz-Kreislauferkrankungen (DZHK), Partner site Munich Heart Alliance, Munich, Germany.
Bruce M PsatyCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA.
Lynda M RoseDivision of Preventive Medicine, Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Jerome I RotterInstitute for Translational Genomics and Population Sciences, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, Calif, USA.
Guenther SilbernagelDepartment of Angiology, Swiss Cardiovascular Centre, Bern University Hospital, Bern, Switzerland.
Jonathan D SmithDepartment of Cellular and Molecular Medicine, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Nona SotoodehniaCardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA.
David J StottInstitute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
Kent D TaylorMedical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
Andreas TomaschitzDepartment of Cardiology, Medical University of Graz, Graz, Austria.
Tatsuhiko TsunodaLaboratory for Medical Science Mathematics, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Andre G UitterlindenDepartment of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
David R Van WagonerDepartment of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Uwe VölkerDZHK (German Centre for Cardiovascular Research), Partner site Greifswald, Germany.
Henry VölzkeDZHK (German Centre for Cardiovascular Research), Partner site Greifswald, Germany.
Joanne M Murabito *Boston University and National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA.
Moritz F Sinner *Department of Medicine I, University Hospital Grosshadern, Ludwig-Maximilians-University, Munich, Germany.
Vilmundur Gudnason *Icelandic Heart Association, Kopavogur Iceland and University of Iceland Reykjavik, Iceland.
Stephan B Felix *Department of Internal Medicine B, University Medicine Greifswald, Greifswald, Germany.
Winfried März *Institute of Public Health, Social and Preventive Medicine, Mannheim Medical Faculty, University of Heidelberg, Mannheim, Germany.
Mina Chung *Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Christine M Albert *Harvard Medical School, Boston, Massachusetts, USA.
Bruno H Stricker *Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
Toshihiro Tanaka *Laboratory for Cardiovascular Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
Susan R Heckbert *Cardiovascular Health Research Unit, Department of Medicine, University of Washington, Seattle, Washington, USA.
J Wouter Jukema *Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands and Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands.
Alvaro Alonso *Division of Epidemiology and Community Health, School of Public Health, University of Minnesota, Minneapolis, USA.
Emelia J Benjamin *Boston University and National Heart, Lung and Blood Institute's Framingham Heart Study, Framingham, Massachusetts, USA.
Patrick T Ellinor *Cardiac Arrhythmia Service, Massachusetts General Hospital, Boston, Massachusetts, USA.
Boston University · USUniversity of Washington · USBrigham and Women's Hospital · USCleveland Clinic · USErasmus MC · NLHarvard University Press · USRIKEN Center for Integrative Medical Sciences · JPUniversity of Glasgow · GBGerman Centre for Cardiovascular Research · DEGroup Health Cooperative · USHelmholtz Zentrum München · DEJohns Hopkins University · USNational Institutes of Health · USUniversitätsmedizin Greifswald · DEUniversity of Iceland · ISCedars-Sinai Medical Center · USDutch Health Care Inspectorate · NLLeeds General Infirmary · GBLeiden University · NLLeiden University Medical Center · NL

Funding

UCLA Clinical and Translational Science InstituteUL1TR000124 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI DUBINETT, STEVEN M. · 2012 to 2015
$57.0M
Transgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI PETER J TONTONOZ · 2003 to 2026
$40.4M
IDENTIFICATION 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
CHARGE Consortium: Omics Discovery for CVD and Aging PhenotypesR01HL105756 · NHLBI · UNIVERSITY OF WASHINGTON · PI Bruce M Psaty, NICHOLAS L SMITH · 2011 to 2026
$9.5M
CLINICAL PROJECT: Age, Gene/Environment Susceptibility Study on the Multi-omics of Aging: A clinical epidemiologic prospective studyZIAAG007380 · NIA · NATIONAL INSTITUTE ON AGING · PI LAUNER, LENORE J · 2009 to 2025
$6.1M
Functional Genomics of Atrial Fibrillation in Human AtriaR01HL111314 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI BARNARD, JOHN, CHUNG, MINA KAY · 2012 to 2019
$6.1M
Genetics of Atrial FibrillationR01HL090620 · NHLBI · CLEVELAND CLINIC LERNER COM-CWRU · PI BARNARD, JOHN, CHUNG, MINA KAY · 2008 to 2012
$2.9M
Genetic Markers of Brain AgingZIAAG007270 · NIA · NATIONAL INSTITUTE ON AGING · PI LAUNER, LENORE J · 2009 to 2025
$2.7M
Mentoring in Arrhythmia ResearchK24HL105780 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI ELLINOR, PATRICK THOMAS · 2011 to 2020
$1.2M
Atrial Fibrillation: Bridging genetic discovery and clinical associationsK23HL114724 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI LUBITZ, STEVEN A · 2013 to 2017
$893k
NCATS NIH HHS UL1 TR000124NHLBI NIH HHS K23 HL114724NHLBI NIH HHS K24 HL105780NHLBI NIH HHS R01 HL090620NHLBI NIH HHS R01 HL092577NHLBI NIH HHS R01 HL105756NHLBI NIH HHS R01 HL111314NIDDK NIH HHS P30 DK063491
6 · The paper itself

Abstract

objectivesThis study sought to identify nonredundant atrial fibrillation (AF) genetic susceptibility signals and examine their cumulative relations with AF risk.

backgroundAF-associated loci span broad genomic regions that may contain multiple susceptibility signals. Whether multiple signals exist at AF loci has not been systematically explored.

methodsWe performed association testing conditioned on the most significant, independently associated genetic markers at 9 established AF loci using 2 complementary techniques in 64,683 individuals of European ancestry (3,869 incident and 3,302 prevalent AF cases). Genetic risk scores were created and tested for association with AF in Europeans and an independent sample of 11,309 individuals of Japanese ancestry (7,916 prevalent AF cases).

resultsWe observed at least 4 distinct AF susceptibility signals on chromosome 4q25 upstream of PITX2, but not at the remaining 8 AF loci. A multilocus score comprised 12 genetic markers demonstrated an estimated 5-fold gradient in AF risk. We observed a similar spectrum of risk associated with these markers in Japanese. Regions containing AF signals on chromosome 4q25 displayed a greater degree of evolutionary conservation than the remainder of the locus, suggesting that they may tag regulatory elements.

conclusionsThe chromosome 4q25 AF locus is architecturally complex and harbors at least 4 AF susceptibility signals in individuals of European ancestry. Similar polygenic AF susceptibility exists between Europeans and Japanese. Future work is necessary to identify causal variants, determine mechanisms by which associated loci predispose to AF, and explore whether AF susceptibility signals classify individuals at risk for AF and related morbidity.

Indexed as

Chromosomes, Human, Pair 4Genetic Predisposition to DiseaseAdultAgedAged, 80 and overAsian PeopleAtrial FibrillationChromosome MappingEuropeFemaleGenetic MarkersHomeobox Protein PITX2Homeodomain ProteinsHumansJapanMaleGenetic MarkersHomeobox Protein PITX2Homeodomain ProteinsTranscription Factorsatrial fibrillationatrial fluttergeneticprognosisrisk

Identifiers

PMID24486271
PMCPMC4009240
OpenAlexW2067359381

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.