Evidence map›Paper›PMID 32429735›Full record

ArticleCirculation2020

Transethnic Genome-Wide Association Study Provides Insights in the Genetic Architecture and Heritability of Long QT Syndrome.

Najim Lahrouchi, Rafik Tadros, Lia Crotti, Yuka Mizusawa, Pieter G Postema, Leander Beekman, Roddy Walsh, Kanae Hasegawa, Julien Barc, Marko Ernsting and 96 more

Erratum issuedOpen access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Circulation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 77 papers, 3 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
77citing papers in PubMed, 3 pooled it
12.1field-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

77 citing papers in PubMed, 3 syntheses or guidelines pooled it, 135 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Trial
  5. Review
  6. Review
  7. Genome-wide association study-identified novel genetic loci for QT interval in Taiwan: implications for population-specific arrhythmia risk.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 · 2026
    Article
  8. Review
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Cardiac arrhythmias and genetics - current stage.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2025
    Article
  16. A heart job: predicting sudden cardiac arrest.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 · 2025
    Article
  17. Article
  18. Genetic QT score as a predictor of sudden cardiac death in participants with sleep-disordered breathing in the UK Biobank.Journal of clinical sleep medicine : JCSM : official publication of the American Academy of Sleep Medicine · 2025
    Article
  19. Review
  20. Article

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

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

106 authors at 20 institutions in 15 countries.

Najim Lahrouchi *Amsterdam UMC, University of Amsterdam, Heart Center; Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, The Netherlands (N.L., R.T., Y.M., P.G.P., L.B., R.W., N.H., H.L.T., A.A.W., C.R.B.).
Rafik Tadros *Amsterdam UMC, University of Amsterdam, Heart Center; Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, The Netherlands (N.L., R.T., Y.M., P.G.P., L.B., R.W., N.H., H.L.T., A.A.W., C.R.B.).
Lia CrottiMember of the European Reference Network for Rare, Low Prevalence, and Complex Diseases of the Heart - ERN GUARD-Heart (N.L., L.C., Y.M., P.G.P., L.B., R.W., J.B., M.E., A.M., U.-B.D., Y.D.W., T.R., R.J., N.H., F.D., G.S.-B., I.D., A.L., C.N., J.-J.S., J.-B.G., J.T.-H., J.B., E.R.B., A.R., S.G.P., H.L.T., P.J.S., E.S.-B., V.P., A.A.W., C.R.B.).
Yuka MizusawaAmsterdam UMC, University of Amsterdam, Heart Center; Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, The Netherlands (N.L., R.T., Y.M., P.G.P., L.B., R.W., N.H., H.L.T., A.A.W., C.R.B.).
Pieter G PostemaAmsterdam UMC, University of Amsterdam, Heart Center; Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, The Netherlands (N.L., R.T., Y.M., P.G.P., L.B., R.W., N.H., H.L.T., A.A.W., C.R.B.).
Leander BeekmanAmsterdam UMC, University of Amsterdam, Heart Center; Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, The Netherlands (N.L., R.T., Y.M., P.G.P., L.B., R.W., N.H., H.L.T., A.A.W., C.R.B.).
Roddy WalshAmsterdam UMC, University of Amsterdam, Heart Center; Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, The Netherlands (N.L., R.T., Y.M., P.G.P., L.B., R.W., N.H., H.L.T., A.A.W., C.R.B.).
Kanae HasegawaDepartment of Cardiovascular Medicine, Shiga University of Medical Science, Otsu, Japan (K.H., S.O., H.I., M.H.).
Julien BarcMember of the European Reference Network for Rare, Low Prevalence, and Complex Diseases of the Heart - ERN GUARD-Heart (N.L., L.C., Y.M., P.G.P., L.B., R.W., J.B., M.E., A.M., U.-B.D., Y.D.W., T.R., R.J., N.H., F.D., G.S.-B., I.D., A.L., C.N., J.-J.S., J.-B.G., J.T.-H., J.B., E.R.B., A.R., S.G.P., H.L.T., P.J.S., E.S.-B., V.P., A.A.W., C.R.B.).
Marko ErnstingMember of the European Reference Network for Rare, Low Prevalence, and Complex Diseases of the Heart - ERN GUARD-Heart (N.L., L.C., Y.M., P.G.P., L.B., R.W., J.B., M.E., A.M., U.-B.D., Y.D.W., T.R., R.J., N.H., F.D., G.S.-B., I.D., A.L., C.N., J.-J.S., J.-B.G., J.T.-H., J.B., E.R.B., A.R., S.G.P., H.L.T., P.J.S., E.S.-B., V.P., A.A.W., C.R.B.).
Kari L TurkowskiDepartments of Cardiovascular Medicine (Division of Heart Rhythm Services and the Windland Smith Rice Genetic Heart Rhythm Clinic), Pediatric and Adolescent Medicine (Division of Pediatric Cardiology), and Molecular Pharmacology & Experimental Therapeutics (Windland Smith Rice Sudden Death Genomics Laboratory), Mayo Clinic, Rochester, MN (K.L.T., D.J.T., J.M.B., M.J.A.).
Andrea MazzantiMember of the European Reference Network for Rare, Low Prevalence, and Complex Diseases of the Heart - ERN GUARD-Heart (N.L., L.C., Y.M., P.G.P., L.B., R.W., J.B., M.E., A.M., U.-B.D., Y.D.W., T.R., R.J., N.H., F.D., G.S.-B., I.D., A.L., C.N., J.-J.S., J.-B.G., J.T.-H., J.B., E.R.B., A.R., S.G.P., H.L.T., P.J.S., E.S.-B., V.P., A.A.W., C.R.B.).
Britt M BeckmannDepartment of Internal Medicine I, University Hospital of the Ludwig Maximilians University, Munich, Germany (B.M.B., M.M.-N., S.K.).
Keiko ShimamotoDepartment of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan (K.S., W.S., T.A.).
Ulla-Britt DiamantMember of the European Reference Network for Rare, Low Prevalence, and Complex Diseases of the Heart - ERN GUARD-Heart (N.L., L.C., Y.M., P.G.P., L.B., R.W., J.B., M.E., A.M., U.-B.D., Y.D.W., T.R., R.J., N.H., F.D., G.S.-B., I.D., A.L., C.N., J.-J.S., J.-B.G., J.T.-H., J.B., E.R.B., A.R., S.G.P., H.L.T., P.J.S., E.S.-B., V.P., A.A.W., C.R.B.).
Yanushi D WijeyeratneMember of the European Reference Network for Rare, Low Prevalence, and Complex Diseases of the Heart - ERN GUARD-Heart (N.L., L.C., Y.M., P.G.P., L.B., R.W., J.B., M.E., A.M., U.-B.D., Y.D.W., T.R., R.J., N.H., F.D., G.S.-B., I.D., A.L., C.N., J.-J.S., J.-B.G., J.T.-H., J.B., E.R.B., A.R., S.G.P., H.L.T., P.J.S., E.S.-B., V.P., A.A.W., C.R.B.).
Yu KuchoNational Hospital Organization Kagoshima Medical Center, Japan (Y.K., M.Y.).
Tomas RobynsMember of the European Reference Network for Rare, Low Prevalence, and Complex Diseases of the Heart - ERN GUARD-Heart (N.L., L.C., Y.M., P.G.P., L.B., R.W., J.B., M.E., A.M., U.-B.D., Y.D.W., T.R., R.J., N.H., F.D., G.S.-B., I.D., A.L., C.N., J.-J.S., J.-B.G., J.T.-H., J.B., E.R.B., A.R., S.G.P., H.L.T., P.J.S., E.S.-B., V.P., A.A.W., C.R.B.).
Taisuke IshikawaOmics Research Center, National Cerebral and Cardiovascular Center, Osaka, Japan (T.I.).
Elena ArbeloCardiovascular Institute, Hospital Clinic de Barcelona, Universitat de Barcelona, Institut d'Investigació August Pi i Sunyer (IDIBAPS), and Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV), Spain (E.A.).
Michael ChristiansenDepartment of Congenital Disorders, Statens Serum Institute, Copenhagen, Denmark (M.C.).
Annika WinboDepartment of Physiology, The University of Auckland, New Zealand (A.W.).
Reza JabbariMember of the European Reference Network for Rare, Low Prevalence, and Complex Diseases of the Heart - ERN GUARD-Heart (N.L., L.C., Y.M., P.G.P., L.B., R.W., J.B., M.E., A.M., U.-B.D., Y.D.W., T.R., R.J., N.H., F.D., G.S.-B., I.D., A.L., C.N., J.-J.S., J.-B.G., J.T.-H., J.B., E.R.B., A.R., S.G.P., H.L.T., P.J.S., E.S.-B., V.P., A.A.W., C.R.B.).
Steven A LubitzCardiac Arrhythmia Service, Massachusetts General Hospital, Boston (S.A.L., P.T.E.).
Johannes SteinfurtDepartment of Cardiology and Angiology I, Heart Center University of Freiburg, Medical Faculty, Germany (J.S., K.E.O.).
Boris RudicDepartment of Medicine, University Medical Center Mannheim, and German Center for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, Germany (B.R., M.B.).
Bart LoeysDepartment of Clinical Genetics, Antwerp University Hospital, Belgium (B.L.).
M Ben ShoemakerDepartment of Medicine (M.B.S., P.E.W., D.M.R.), Vanderbilt University Medical Center, Nashville, TN.
Peter E WeekeThe Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Denmark (R.J., P.E.W., J.T.-H.).
Ryan PfeifferMasonic Medical Research Institute, Utica, NY (R.P.).
Brianna DaviesHeart Rhythm Services, Division of Cardiology, Department of Medicine, University of British Columbia, Vancouver, Canada (B.D., A.D.K.).
Antoine AndorinMolecular and Clinical Sciences Research Institute, St George's University of London and Cardiology Clinical Academic Group, St George's University Hospitals NHS Foundation Trust, United Kingdom (Y.D.W., A.A., E.R.B.).
Nynke HofmanAmsterdam UMC, University of Amsterdam, Heart Center; Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, The Netherlands (N.L., R.T., Y.M., P.G.P., L.B., R.W., N.H., H.L.T., A.A.W., C.R.B.).
Federica DagradiMember of the European Reference Network for Rare, Low Prevalence, and Complex Diseases of the Heart - ERN GUARD-Heart (N.L., L.C., Y.M., P.G.P., L.B., R.W., J.B., M.E., A.M., U.-B.D., Y.D.W., T.R., R.J., N.H., F.D., G.S.-B., I.D., A.L., C.N., J.-J.S., J.-B.G., J.T.-H., J.B., E.R.B., A.R., S.G.P., H.L.T., P.J.S., E.S.-B., V.P., A.A.W., C.R.B.).
Matteo PedrazziniLaboratory of Cardiovascular Genetics (L.C., M.P., P.J.S.), Istituto Auxologico Italiano, IRCCS, Milan, Italy.
David J TesterDepartments of Cardiovascular Medicine (Division of Heart Rhythm Services and the Windland Smith Rice Genetic Heart Rhythm Clinic), Pediatric and Adolescent Medicine (Division of Pediatric Cardiology), and Molecular Pharmacology & Experimental Therapeutics (Windland Smith Rice Sudden Death Genomics Laboratory), Mayo Clinic, Rochester, MN (K.L.T., D.J.T., J.M.B., M.J.A.).
J Martijn BosDepartments of Cardiovascular Medicine (Division of Heart Rhythm Services and the Windland Smith Rice Genetic Heart Rhythm Clinic), Pediatric and Adolescent Medicine (Division of Pediatric Cardiology), and Molecular Pharmacology & Experimental Therapeutics (Windland Smith Rice Sudden Death Genomics Laboratory), Mayo Clinic, Rochester, MN (K.L.T., D.J.T., J.M.B., M.J.A.).
Georgia Sarquella-BrugadaMember of the European Reference Network for Rare, Low Prevalence, and Complex Diseases of the Heart - ERN GUARD-Heart (N.L., L.C., Y.M., P.G.P., L.B., R.W., J.B., M.E., A.M., U.-B.D., Y.D.W., T.R., R.J., N.H., F.D., G.S.-B., I.D., A.L., C.N., J.-J.S., J.-B.G., J.T.-H., J.B., E.R.B., A.R., S.G.P., H.L.T., P.J.S., E.S.-B., V.P., A.A.W., C.R.B.).
Óscar CampuzanoCardiovascular Program, Research Institute of Sant Joan de Déu (IRSJD), Barcelona, Spain (G.S.-B., O.C.).
Pyotr G PlatonovCenter for Integrative Electrocardiology (CIEL), Department of Cardiology, Clinical Sciences, Lund University, Sweden (P.G.P.).
Birgit StallmeyerInstitute for Genetics of Heart Diseases, Department of Cardiovascular Medicine, University Hospital Muenster, Germany (M.E., B.S., S.Z., E.S.-B.).
Sven ZumhagenInstitute for Genetics of Heart Diseases, Department of Cardiovascular Medicine, University Hospital Muenster, Germany (M.E., B.S., S.Z., E.S.-B.).
Eline A NannenbergDepartment of Clinical Genetics, Amsterdam UMC, University of Amsterdam, The Netherlands (E.A.N., J.P.v.T.).
Jan H VeldinkDepartment of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, The Netherlands (J.H.V., L.H.v.d.B.).
Leonard H van den BergDepartment of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, The Netherlands (J.H.V., L.H.v.d.B.).
Ammar Al-ChalabiKing's College Hospital, Bessemer Road, London, United Kingdom (A.A.-C.).
Christopher E ShawDepartment of Basic and Clinical Neuroscience, King's College London, Maurice Wohl Clinical Neuroscience Institute, United Kingdom (A.A.-C., C.E.S.).
Pamela J ShawCenter for Cardiac Arrhythmias of Genetic Origin (L.C., F.D., P.J.S.), Istituto Auxologico Italiano, IRCCS, Milan, Italy.
Karen E MorrisonFaculty of Medicine, University of Southampton, University Hospital Southampton, United Kingdom (K.E.M.).
Peter M AndersenDepartment of Neurology, Ulm University, Germany (P.M.A.).
Martina Müller-NurasyidDepartment of Internal Medicine I, University Hospital of the Ludwig Maximilians University, Munich, Germany (B.M.B., M.M.-N., S.K.).
Daniele CusiDepartment of Health Sciences, University of Milan, Italy (D.C., C.B.).
Cristina BarlassinaDepartment of Health Sciences, University of Milan, Italy (D.C., C.B.).
Pilar GalanEquipe de Recherche en Epidémiologie Nutritionnelle, Centre d'Epidémiologie et Statistiques Paris Cité, Université Paris 13, Inserm (U1153), Inra (U1125), COMUE Sorbonne-Paris-Cité, Bobigny, France (P.G.).
Mark LathropMcGill University and Génome Québec Innovation Centre, Montréal, Canada (M.L., M.M.).
Markus MunterMcGill University and Génome Québec Innovation Centre, Montréal, Canada (M.L., M.M.).
Thomas WergeThe Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen, Denmark (T.W.).
Marta RibasésPsychiatric Genetics Unit, Institute Vall d'Hebron Research (VHIR), Universitat Autònoma de Barcelona, Spain (M.R.).
Tin AungSingapore Eye Research Institute (T.A.).
Chiea C KhorGenome Institute of Singapore (C.C.K.).
Mineo OzakiOzaki Eye Hospital, Miyazaki, Japan (M.O.).
Peter LichtnerInstitute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany (P.L., T.M.).
Thomas MeitingerInstitute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany (P.L., T.M.).
J Peter van TintelenDepartment of Clinical Genetics, Amsterdam UMC, University of Amsterdam, The Netherlands (E.A.N., J.P.v.T.).
Yvonne HoedemaekersDepartment of Clinical Genetics, University Medical Centre Groningen, The Netherlands (J.P.v.T., Y.H.).
Isabelle DenjoyMember of the European Reference Network for Rare, Low Prevalence, and Complex Diseases of the Heart - ERN GUARD-Heart (N.L., L.C., Y.M., P.G.P., L.B., R.W., J.B., M.E., A.M., U.-B.D., Y.D.W., T.R., R.J., N.H., F.D., G.S.-B., I.D., A.L., C.N., J.-J.S., J.-B.G., J.T.-H., J.B., E.R.B., A.R., S.G.P., H.L.T., P.J.S., E.S.-B., V.P., A.A.W., C.R.B.).
Antoine LeenhardtMember of the European Reference Network for Rare, Low Prevalence, and Complex Diseases of the Heart - ERN GUARD-Heart (N.L., L.C., Y.M., P.G.P., L.B., R.W., J.B., M.E., A.M., U.-B.D., Y.D.W., T.R., R.J., N.H., F.D., G.S.-B., I.D., A.L., C.N., J.-J.S., J.-B.G., J.T.-H., J.B., E.R.B., A.R., S.G.P., H.L.T., P.J.S., E.S.-B., V.P., A.A.W., C.R.B.).
Carlo NapolitanoMember of the European Reference Network for Rare, Low Prevalence, and Complex Diseases of the Heart - ERN GUARD-Heart (N.L., L.C., Y.M., P.G.P., L.B., R.W., J.B., M.E., A.M., U.-B.D., Y.D.W., T.R., R.J., N.H., F.D., G.S.-B., I.D., A.L., C.N., J.-J.S., J.-B.G., J.T.-H., J.B., E.R.B., A.R., S.G.P., H.L.T., P.J.S., E.S.-B., V.P., A.A.W., C.R.B.).
Wataru ShimizuDepartment of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan (K.S., W.S., T.A.).
Jean-Jacques SchottMember of the European Reference Network for Rare, Low Prevalence, and Complex Diseases of the Heart - ERN GUARD-Heart (N.L., L.C., Y.M., P.G.P., L.B., R.W., J.B., M.E., A.M., U.-B.D., Y.D.W., T.R., R.J., N.H., F.D., G.S.-B., I.D., A.L., C.N., J.-J.S., J.-B.G., J.T.-H., J.B., E.R.B., A.R., S.G.P., H.L.T., P.J.S., E.S.-B., V.P., A.A.W., C.R.B.).
Jean-Baptiste GourraudMember of the European Reference Network for Rare, Low Prevalence, and Complex Diseases of the Heart - ERN GUARD-Heart (N.L., L.C., Y.M., P.G.P., L.B., R.W., J.B., M.E., A.M., U.-B.D., Y.D.W., T.R., R.J., N.H., F.D., G.S.-B., I.D., A.L., C.N., J.-J.S., J.-B.G., J.T.-H., J.B., E.R.B., A.R., S.G.P., H.L.T., P.J.S., E.S.-B., V.P., A.A.W., C.R.B.).
Takeru MakiyamaDepartment of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Japan (T.M.).
Seiko OhnoDepartment of Cardiovascular Medicine, Shiga University of Medical Science, Otsu, Japan (K.H., S.O., H.I., M.H.).
Hideki ItohDepartment of Cardiovascular Medicine, Shiga University of Medical Science, Otsu, Japan (K.H., S.O., H.I., M.H.).
Andrew D KrahnHeart Rhythm Services, Division of Cardiology, Department of Medicine, University of British Columbia, Vancouver, Canada (B.D., A.D.K.).
Charles AntzelevitchLankenau Institute for Medical Research and Lankenau Heart Institute, Wynnewood, PA (C.A.).
Dan M RodenDepartment of Biomedical Informatics (D.M.R.), Vanderbilt University Medical Center, Nashville, TN.
Johan SaenenDepartment of Cardiology, Antwerp University Hospital, Belgium (J.S.).
Martin BorggrefeDepartment of Medicine, University Medical Center Mannheim, and German Center for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, Germany (B.R., M.B.).
Katja E OdeningDepartment of Cardiology and Angiology I, Heart Center University of Freiburg, Medical Faculty, Germany (J.S., K.E.O.).
Patrick T EllinorCardiac Arrhythmia Service, Massachusetts General Hospital, Boston (S.A.L., P.T.E.).
Jacob Tfelt-HansenMember of the European Reference Network for Rare, Low Prevalence, and Complex Diseases of the Heart - ERN GUARD-Heart (N.L., L.C., Y.M., P.G.P., L.B., R.W., J.B., M.E., A.M., U.-B.D., Y.D.W., T.R., R.J., N.H., F.D., G.S.-B., I.D., A.L., C.N., J.-J.S., J.-B.G., J.T.-H., J.B., E.R.B., A.R., S.G.P., H.L.T., P.J.S., E.S.-B., V.P., A.A.W., C.R.B.).
Jonathan R SkinnerCardiac Inherited Disease Group, Starship Children's Hospital, Auckland, New Zealand (J.R.S.).
Maarten P van den BergDepartment of Cardiology, University Medical Center Groningen, University of Groningen, The Netherlands (M.P.v.d.B.).
Morten Salling OlesenLaboratory for Molecular Cardiology, Department of Cardiology, The Heart Centre, Rigshospitalet (Copenhagen University Hospital), Denmark (M.S.O.).
Josep BrugadaMember of the European Reference Network for Rare, Low Prevalence, and Complex Diseases of the Heart - ERN GUARD-Heart (N.L., L.C., Y.M., P.G.P., L.B., R.W., J.B., M.E., A.M., U.-B.D., Y.D.W., T.R., R.J., N.H., F.D., G.S.-B., I.D., A.L., C.N., J.-J.S., J.-B.G., J.T.-H., J.B., E.R.B., A.R., S.G.P., H.L.T., P.J.S., E.S.-B., V.P., A.A.W., C.R.B.).
Ramón BrugadaCenter for Biomedical Diagnosis, Hospital Clinic de Barcelona, Universitat de Barcelona; Institut d'Investigació August Pi i Sunyer (IDIBAPS); Cardiovascular Genetics Center, University of Girona-IDIBGI; and Medical Science Department, School of Medicine, University of Girona, Spain (O.C., R.B.).
Naomasa MakitaNational Cerebral and Cardiovascular Center Research Institute, Osaka, Japan (N.M.).
Jeroen BreckpotCentre for Human Genetics, University Hospitals Leuven, Belgium (J.B.).
Masao YoshinagaNational Hospital Organization Kagoshima Medical Center, Japan (Y.K., M.Y.).
Elijah R BehrMember of the European Reference Network for Rare, Low Prevalence, and Complex Diseases of the Heart - ERN GUARD-Heart (N.L., L.C., Y.M., P.G.P., L.B., R.W., J.B., M.E., A.M., U.-B.D., Y.D.W., T.R., R.J., N.H., F.D., G.S.-B., I.D., A.L., C.N., J.-J.S., J.-B.G., J.T.-H., J.B., E.R.B., A.R., S.G.P., H.L.T., P.J.S., E.S.-B., V.P., A.A.W., C.R.B.).
Annika RydbergMember of the European Reference Network for Rare, Low Prevalence, and Complex Diseases of the Heart - ERN GUARD-Heart (N.L., L.C., Y.M., P.G.P., L.B., R.W., J.B., M.E., A.M., U.-B.D., Y.D.W., T.R., R.J., N.H., F.D., G.S.-B., I.D., A.L., C.N., J.-J.S., J.-B.G., J.T.-H., J.B., E.R.B., A.R., S.G.P., H.L.T., P.J.S., E.S.-B., V.P., A.A.W., C.R.B.).
Takeshi AibaDepartment of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan (K.S., W.S., T.A.).
Stefan KääbDepartment of Internal Medicine I, University Hospital of the Ludwig Maximilians University, Munich, Germany (B.M.B., M.M.-N., S.K.).
Silvia G PrioriMember of the European Reference Network for Rare, Low Prevalence, and Complex Diseases of the Heart - ERN GUARD-Heart (N.L., L.C., Y.M., P.G.P., L.B., R.W., J.B., M.E., A.M., U.-B.D., Y.D.W., T.R., R.J., N.H., F.D., G.S.-B., I.D., A.L., C.N., J.-J.S., J.-B.G., J.T.-H., J.B., E.R.B., A.R., S.G.P., H.L.T., P.J.S., E.S.-B., V.P., A.A.W., C.R.B.).
Pascale GuicheneyINSERM, Sorbonne University, UMRS 1166, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France (P.G.).
Hanno L TanAmsterdam UMC, University of Amsterdam, Heart Center; Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, The Netherlands (N.L., R.T., Y.M., P.G.P., L.B., R.W., N.H., H.L.T., A.A.W., C.R.B.).
Christopher Newton-ChehCardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston (C.N.-C.).
Michael J AckermanDepartments of Cardiovascular Medicine (Division of Heart Rhythm Services and the Windland Smith Rice Genetic Heart Rhythm Clinic), Pediatric and Adolescent Medicine (Division of Pediatric Cardiology), and Molecular Pharmacology & Experimental Therapeutics (Windland Smith Rice Sudden Death Genomics Laboratory), Mayo Clinic, Rochester, MN (K.L.T., D.J.T., J.M.B., M.J.A.).
Peter J SchwartzMember of the European Reference Network for Rare, Low Prevalence, and Complex Diseases of the Heart - ERN GUARD-Heart (N.L., L.C., Y.M., P.G.P., L.B., R.W., J.B., M.E., A.M., U.-B.D., Y.D.W., T.R., R.J., N.H., F.D., G.S.-B., I.D., A.L., C.N., J.-J.S., J.-B.G., J.T.-H., J.B., E.R.B., A.R., S.G.P., H.L.T., P.J.S., E.S.-B., V.P., A.A.W., C.R.B.).
Eric Schulze-BahrMember of the European Reference Network for Rare, Low Prevalence, and Complex Diseases of the Heart - ERN GUARD-Heart (N.L., L.C., Y.M., P.G.P., L.B., R.W., J.B., M.E., A.M., U.-B.D., Y.D.W., T.R., R.J., N.H., F.D., G.S.-B., I.D., A.L., C.N., J.-J.S., J.-B.G., J.T.-H., J.B., E.R.B., A.R., S.G.P., H.L.T., P.J.S., E.S.-B., V.P., A.A.W., C.R.B.).
Vincent ProbstMember of the European Reference Network for Rare, Low Prevalence, and Complex Diseases of the Heart - ERN GUARD-Heart (N.L., L.C., Y.M., P.G.P., L.B., R.W., J.B., M.E., A.M., U.-B.D., Y.D.W., T.R., R.J., N.H., F.D., G.S.-B., I.D., A.L., C.N., J.-J.S., J.-B.G., J.T.-H., J.B., E.R.B., A.R., S.G.P., H.L.T., P.J.S., E.S.-B., V.P., A.A.W., C.R.B.).
Minoru HorieDepartment of Cardiovascular Medicine, Shiga University of Medical Science, Otsu, Japan (K.H., S.O., H.I., M.H.).
Arthur A WildeAmsterdam UMC, University of Amsterdam, Heart Center; Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, The Netherlands (N.L., R.T., Y.M., P.G.P., L.B., R.W., N.H., H.L.T., A.A.W., C.R.B.).
Michael W T TanckDepartment of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC, University of Amsterdam, The Netherlands (M.W.T.T.).
Connie R BezzinaAmsterdam UMC, University of Amsterdam, Heart Center; Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, The Netherlands (N.L., R.T., Y.M., P.G.P., L.B., R.W., N.H., H.L.T., A.A.W., C.R.B.).
Amsterdam Neuroscience · NLHeart Rhythm Society · USERN GUARD-Heart · NLNational Cerebral and Cardiovascular Center · JPCentre National de la Recherche Scientifique · FRInserm · FRIRCCS Istituto Auxologico Italiano · ITUniversity Hospital Münster · DEHelmholtz Zentrum München · DEIstituti Clinici Scientifici Maugeri · ITShiga University of Medical Science · JPSt George’s University Hospitals NHS Foundation Trust · GBUniversity Medical Center Groningen · NLUniversity of Copenhagen · DKAntwerp University Hospital · BEBroad Institute · USCopenhagen University Hospital · DKHeidelberg University · DEKagoshima Medical Center · JPLudwig-Maximilians-Universität München · DE

Funding

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
Understanding and preventing HLA-associated drug reactionsP50GM115305 · NIGMS · VANDERBILT UNIVERSITY MEDICAL CENTER · PI DENNY, JOSHUA C. · 2015 to 2019
$13.0M
NRSA Training CoreTL1TR002380 · NCATS · MAYO CLINIC ROCHESTER · PI Felicity T. B. Enders, ANTHONY John WINDEBANK · 2017 to 2026
$6.0M
Genomics of Cardiac ArrhythmiasR01HL139731 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI ELLINOR, PATRICK THOMAS · 2018 to 2022
$3.3M
AFGen Consortium: Atrial Fibrillation Genomics to Functional AnalysesR01HL128914 · NHLBI · BOSTON UNIVERSITY MEDICAL CAMPUS · PI BENJAMIN, EMELIA J., ELLINOR, PATRICK THOMAS · 2015 to 2018
$3.1M
Mentoring in Arrhythmia ResearchK24HL105780 · NHLBI · MASSACHUSETTS GENERAL HOSPITAL · PI ELLINOR, PATRICK THOMAS · 2011 to 2020
$1.2M
Atrial Fibrillation Susceptibility Due to Genetic Variation at Chromosome 4q25K23HL127704 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI SHOEMAKER, MOORE BENJAMIN · 2015 to 2019
$869k
Medical Research Council G0600974Medical Research Council MR/L501529/1Medical Research Council MR/R024804/1NCATS NIH HHS TL1 TR002380NHLBI NIH HHS K23 HL127704NHLBI NIH HHS K24 HL105780NHLBI NIH HHS R01 HL092577NHLBI NIH HHS R01 HL128914NHLBI NIH HHS R01 HL139731NIGMS NIH HHS P50 GM115305
6 · The paper itself

Abstract

backgroundLong QT syndrome (LQTS) is a rare genetic disorder and a major preventable cause of sudden cardiac death in the young. A causal rare genetic variant with large effect size is identified in up to 80% of probands (genotype positive) and cascade family screening shows incomplete penetrance of genetic variants. Furthermore, a proportion of cases meeting diagnostic criteria for LQTS remain genetically elusive despite genetic testing of established genes (genotype negative). These observations raise the possibility that common genetic variants with small effect size contribute to the clinical picture of LQTS. This study aimed to characterize and quantify the contribution of common genetic variation to LQTS disease susceptibility.

methodsWe conducted genome-wide association studies followed by transethnic meta-analysis in 1656 unrelated patients with LQTS of European or Japanese ancestry and 9890 controls to identify susceptibility single nucleotide polymorphisms. We estimated the common variant heritability of LQTS and tested the genetic correlation between LQTS susceptibility and other cardiac traits. Furthermore, we tested the aggregate effect of the 68 single nucleotide polymorphisms previously associated with the QT-interval in the general population using a polygenic risk score.

resultsGenome-wide association analysis identified 3 loci associated with LQTS at genome-wide statistical significance (

conclusionsThis work establishes an important role for common genetic variation in susceptibility to LQTS. We demonstrate overlap between genetic control of the QT-interval in the general population and genetic factors contributing to LQTS susceptibility. Using polygenic risk score analyses aggregating common genetic variants that modulate the QT-interval in the general population, we provide evidence for a polygenic architecture in genotype negative LQTS.

Indexed as

Genetic Predisposition to DiseaseGenome-Wide Association StudyAdolescentAdultAge of OnsetAllelesCase-Control StudiesElectrocardiographyGenetic Association StudiesGenotypeHumansLong QT SyndromeMultifactorial InheritancePhenotypePolymorphism, Single NucleotidePrognosisgenome-wide association studyinheritance patternslong QT syndrome

Identifiers

PMID32429735
PMCPMC7382531
OpenAlexW3027724762

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

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.