Transethnic Genome-Wide Association Study Provides Insights in the Genetic Architecture and Heritability of Long QT Syndrome
Por:
Lahrouchi N, Tadros R, Crotti L, Mizusawa Y, Postema PG, Beekman L, Walsh R, Hasegawa K, Barc J, Ernsting M, Turkowski KL, Mazzanti A, Beckmann BM, Shimamoto K, Diamant UB, Wijeyeratne YD, Kucho Y, Robyns T, Ishikawa T, Arbelo E, Christiansen M, Winbo A, Jabbari R, Lubitz SA, Steinfurt J, Rudic B, Loeys B, Shoemaker MB, Weeke PE, Pfeiffer R, Davies B, Andorin A, Hofman N, Dagradi F, Pedrazzini M, Tester DJ, Bos JM, Sarquella-Brugada G, Campuzano Ó, Platonov PG, Stallmeyer B, Zumhagen S, Nannenberg EA, Veldink JH, van den Berg LH, Al-Chalabi A, Shaw CE, Shaw PJ, Morrison KE, Andersen PM, Müller-Nurasyid M, Cusi D, Barlassina C, Galan P, Lathrop M, Munter M, Werge T, Ribasés M, Aung T, Khor CC, Ozaki M, Lichtner P, Meitinger T, van Tintelen JP, Hoedemaekers Y, Denjoy I, Leenhardt A, Napolitano C, Shimizu W, Schott JJ, Gourraud JB, Makiyama T, Ohno S, Itoh H, Krahn AD, Antzelevitch C, Roden DM, Saenen J, Borggrefe M, Odening KE, Ellinor PT, Tfelt-Hansen J, Skinner JR, van den Berg MP, Olesen MS, Brugada-Terradellas J, Brugada R, Makita N, Breckpot J, Yoshinaga M, Behr ER, Rydberg A, Aiba T, Kääb S, Priori SG, Guicheney P, Tan HL, Newton-Cheh C, Ackerman MJ, Schwartz PJ, Schulze-Bahr E, Probst V, Horie M, Wilde AA, Tanck MWT and Bezzina CR
Publicada:
28 jul 2020
Ahead of Print:
20 may 2020
Resumen:
Background: Long 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. Methods: We 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. Results: Genome-wide association analysis identified 3 loci associated with LQTS at genome-wide statistical significance (P<5x10(-8)) nearNOS1AP,KCNQ1, andKLF12, and 1 missense variant inKCNE1(p.Asp85Asn) at the suggestive threshold (P<10(-6)). Heritability analyses showed that approximate to 15% of variance in overall LQTS susceptibility was attributable to common genetic variation (h2SNP0.148; standard error 0.019). LQTS susceptibility showed a strong genome-wide genetic correlation with the QT-interval in the general population (r(g)=0.40;P=3.2x10(-3)). The polygenic risk score comprising common variants previously associated with the QT-interval in the general population was greater in LQTS cases compared with controls (P<10-13), and it is notable that, among patients with LQTS, this polygenic risk score was greater in patients who were genotype negative compared with those who were genotype positive (P<0.005). Conclusions: This 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.
Filiaciones:
Lahrouchi N:
Amsterdam UMC, University of Amsterdam, Heart Center
Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, Meibergdreef 9, Amsterdam, The Netherlands
Member of the European Reference Network for rare, low prevalence and complex diseases of the heart - ERN GUARD-Heart
Tadros R:
Amsterdam UMC, University of Amsterdam, Heart Center
Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, Meibergdreef 9, Amsterdam, The Netherlands
Cardiovascular Genetics Center, Montreal Heart Institute and Faculty of Medicine, Université de Montréal, Montreal, Canada
Crotti L:
Member of the European Reference Network for rare, low prevalence and complex diseases of the heart - ERN GUARD-Heart
Istituto Auxologico Italiano, IRCCS, Center for Cardiac Arrhythmias of Genetic Origin, Milan, Italy
Istituto Auxologico Italiano, IRCCS, Laboratory of Cardiovascular Genetics, Milan, Italy
Istituto Auxologico Italiano, IRCCS, Department of Cardiovascular, Neural and Metabolic Sciences, San Luca Hospital, Milan, Italy
Department of Medicine and Surgery, University of Milano-Bicocca, Milan, Italy
Mizusawa Y:
Amsterdam UMC, University of Amsterdam, Heart Center
Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, Meibergdreef 9, Amsterdam, The Netherlands
Member of the European Reference Network for rare, low prevalence and complex diseases of the heart - ERN GUARD-Heart
Postema PG:
Amsterdam UMC, University of Amsterdam, Heart Center
Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, Meibergdreef 9, Amsterdam, The Netherlands
Member of the European Reference Network for rare, low prevalence and complex diseases of the heart - ERN GUARD-Heart
Beekman L:
Amsterdam UMC, University of Amsterdam, Heart Center
Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, Meibergdreef 9, Amsterdam, The Netherlands
Member of the European Reference Network for rare, low prevalence and complex diseases of the heart - ERN GUARD-Heart
Walsh R:
Amsterdam UMC, University of Amsterdam, Heart Center
Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, Meibergdreef 9, Amsterdam, The Netherlands
Member of the European Reference Network for rare, low prevalence and complex diseases of the heart - ERN GUARD-Heart
Hasegawa K:
Department of Cardiovascular Medicine, Shiga University of Medical Science, Otsu, Japan
Department of Cardiovascular Medicine, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
Barc J:
Member of the European Reference Network for rare, low prevalence and complex diseases of the heart - ERN GUARD-Heart
l'institut du thorax, INSERM, CNRS, Univ Nantes, Nantes, France
Ernsting M:
Member of the European Reference Network for rare, low prevalence and complex diseases of the heart - ERN GUARD-Heart
Institute for Genetics of Heart Diseases, Department of Cardiovascular Medicine, University Hospital Muenster, Muenster, Germany
Turkowski KL:
Departments 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
Mazzanti A:
Member of the European Reference Network for rare, low prevalence and complex diseases of the heart - ERN GUARD-Heart
Molecular Cardiology, ICS Maugeri, IRCCS and Department of Molecular Medicine, University of Pavia, Pavia, Italy
Beckmann BM:
Department of Internal Medicine I, University Hospital of the Ludwig Maximilians University, Munich, Germany
Shimamoto K:
Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan
Diamant UB:
Member of the European Reference Network for rare, low prevalence and complex diseases of the heart - ERN GUARD-Heart
Department of Clinical Sciences, Unit of Paediatrics, Umeå University, Umeå, Sweden
Wijeyeratne YD:
Member of the European Reference Network for rare, low prevalence and complex diseases of the heart - ERN GUARD-Heart
Molecular and Clinical Sciences Research Institute, St George's University of London, London, United Kingdom
Cardiology Clinical Academic Group, St George's University Hospitals NHS Foundation Trust, London, United Kingdom
Kucho Y:
National Hospital Organization Kagoshima Medical Center, Japan
Robyns T:
Member of the European Reference Network for rare, low prevalence and complex diseases of the heart - ERN GUARD-Heart
Department of Cardiovascular Diseases, University Hospitals Leuven, Belgium
Department of cardiovascular sciences, KU Leuven, Belgium
Ishikawa T:
Omics Research Center, National Cerebral and Cardiovascular Center, Osaka, Japan
Arbelo E:
Cardiovascular Institute, Hospital Clinic de Barcelona, Universitat de Barcelona, Spain. Institut d'Investigació August Pi i Sunyer (IDIBAPS). Centro de Investigacion Biomedica en Red de Enfermedades Cardiovasculares (CIBERCV), Barcelona, Spain
Christiansen M:
Department of Congenital Disorders, Statens Serum Institute, Copenhagen, Denmark
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen, Denmark
Laboratory of Experimental Cardiology, Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
Winbo A:
Department of Physiology, The University of Auckland, Auckland, New Zealand
Jabbari R:
Member of the European Reference Network for rare, low prevalence and complex diseases of the heart - ERN GUARD-Heart
The Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
Lubitz SA:
Cardiac Arrhythmia Service, Massachusetts General Hospital, Boston, MA
Cardiovascular Disease Initiative and Program in Medical and Population Genetics, Broad Institute, Cambridge, Boston, MA
Steinfurt J:
Department of Cardiology and Angiology I, Heart Center University of Freiburg, Medical Faculty, Freiburg, Germany
Rudic B:
Department of Medicine, University Medical Center Mannheim, Mannheim, Germany
German Center for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, Germany
Loeys B:
Department of Clinical Genetics, Antwerp University Hospital, Antwerp, Belgium
Shoemaker MB:
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
Weeke PE:
The Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
Pfeiffer R:
Masonic Medical Research Institute, Utica, NY
Davies B:
Heart Rhythm Services, Division of Cardiology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
Andorin A:
Molecular and Clinical Sciences Research Institute, St George's University of London, London, United Kingdom
Cardiology Clinical Academic Group, St George's University Hospitals NHS Foundation Trust, London, United Kingdom
l'institut du thorax, CHU Nantes, Service de Cardiologie, Nantes, France
Hofman N:
Amsterdam UMC, University of Amsterdam, Heart Center
Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, Meibergdreef 9, Amsterdam, The Netherlands
Member of the European Reference Network for rare, low prevalence and complex diseases of the heart - ERN GUARD-Heart
Dagradi F:
Member of the European Reference Network for rare, low prevalence and complex diseases of the heart - ERN GUARD-Heart
Istituto Auxologico Italiano, IRCCS, Center for Cardiac Arrhythmias of Genetic Origin, Milan, Italy
Pedrazzini M:
Istituto Auxologico Italiano, IRCCS, Laboratory of Cardiovascular Genetics, Milan, Italy
Tester DJ:
Departments 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
Bos JM:
Departments 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
Sarquella-Brugada G:
Member of the European Reference Network for rare, low prevalence and complex diseases of the heart - ERN GUARD-Heart
Arrhythmia, Inherited Heart Disease and Sudden Death Unit, Hospital Sant Joan de Déu, European Reference Center at the ERN GUARD-Heart Reference Network for Rare Cardiac Diseases, Barcelona, Spain
Medical Science Department, School of Medicine, University of Girona, Girona, Spain
Cardiovascular Program, Research Institute of Sant Joan de Déu (IRSJD), Barcelona, Spain
Campuzano Ó:
Cardiovascular Program, Research Institute of Sant Joan de Déu (IRSJD), Barcelona, Spain
Center for Biomedical Diagnosis, Hospital Clinic de Barcelona, Universitat de Barcelona, Spain. Institut d'Investigació August Pi i Sunyer (IDIBAPS). Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona (Spain). Medical Science Department, School of Medicine, University of Girona, Girona, Spain
Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Madrid, Spain
Platonov PG:
Center for Integrative Electrocardiology (CIEL), Department of Cardiology, Clinical Sciences, Lund University, Lund, Sweden
Stallmeyer B:
Institute for Genetics of Heart Diseases, Department of Cardiovascular Medicine, University Hospital Muenster, Muenster, Germany
Zumhagen S:
Institute for Genetics of Heart Diseases, Department of Cardiovascular Medicine, University Hospital Muenster, Muenster, Germany
Nannenberg EA:
Department of Clinical Genetics, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
Veldink JH:
Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands
van den Berg LH:
Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands
Al-Chalabi A:
King's College Hospital, Bessemer Road, London, SE5 9RS, UK
Department of Basic and Clinical Neuroscience, King's College London, Maurice Wohl Clinical Neuroscience Institute, London, UK
Shaw CE:
Department of Basic and Clinical Neuroscience, King's College London, Maurice Wohl Clinical Neuroscience Institute, London, UK
UK Dementia Research Institute, King's College London, London, UK
Shaw PJ:
Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK
Morrison KE:
Faculty of Medicine, University of Southampton, University Hospital Southampton, Southampton, UK
Andersen PM:
Department of Neurology, Ulm University, 89081 Ulm, Germany
and Department of Pharmacology and Clinical Neuroscience, Umeå University, 90187 Umeå, Sweden
Müller-Nurasyid M:
Department of Internal Medicine I, University Hospital of the Ludwig Maximilians University, Munich, Germany
Institute of Genetic Epidemiology, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany
Chair of Genetic Epidemiology, IBE, Faculty of Medicine, LMU Munich, Germany
Cusi D:
Department of Health Sciences, University of Milan, Milan, Italy
Bio4Dreams - business nursery for life sciences, Milan, Italy
Barlassina C:
Department of Health Sciences, University of Milan, Milan, Italy
Bio4Dreams - business nursery for life sciences, Milan, Italy
Galan P:
Equipe de Recherche en Epidémiologie Nutritionnelle, Centre d'Epidémiologie et Statistiques Paris Cité, Université Paris 13, Inserm (U1153), Inra (U1125), COMUE SorbonneParis-Cité, Bobigny, France
Lathrop M:
McGill University and Génome Québec Innovation Centre, Montréal, Québec, Canada
Munter M:
McGill University and Génome Québec Innovation Centre, Montréal, Québec, Canada
Werge T:
The Lundbeck Foundation Initiative for Integrative Psychiatric Research, iPSYCH, Copenhagen, Denmark
Institute of Biological Psychiatry, Mental Health Centre Sct Hans, Copenhagen University Hospital, Roskilde, Denmark
Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
Ribasés M:
Psychiatric Genetics Unit, Institute Vall d'Hebron Research (VHIR), Universitat Autònoma de Barcelona, Barcelona, Spain
Aung T:
Singapore Eye Research Institute, Singapore, Singapore
Khor CC:
Genome Institute of Singapore, Singapore, Singapore
Ozaki M:
Ozaki Eye Hospital, 1-15, Kamezaki, Hyuga, Miyazaki 883-0066 Japan
Lichtner P:
Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany
Meitinger T:
Institute of Human Genetics, Helmholtz Zentrum München, Neuherberg, Germany
van Tintelen JP:
Department of Clinical Genetics, Amsterdam UMC, University of Amsterdam, Amsterdam, the Netherlands
Department of Clinical Genetics, University Medical Centre Groningen, Groningen, The Netherlands
Department of Clinical Genetics, University Medical Centre Utrecht, University of Utrecht, Utrecht, The Netherlands
Hoedemaekers Y:
Department of Clinical Genetics, University Medical Centre Groningen, Groningen, The Netherlands
Denjoy I:
Member of the European Reference Network for rare, low prevalence and complex diseases of the heart - ERN GUARD-Heart
AP-HP, Hôpital Bichat, Département de Cardiologie et Centre de Référence des Maladies Cardiaques Héréditaires, F-75018 Paris, France, Université de Paris INSERM U1166, F-75013 Paris, France
Leenhardt A:
Member of the European Reference Network for rare, low prevalence and complex diseases of the heart - ERN GUARD-Heart
AP-HP, Hôpital Bichat, Département de Cardiologie et Centre de Référence des Maladies Cardiaques Héréditaires, F-75018 Paris, France, Université de Paris INSERM U1166, F-75013 Paris, France
Napolitano C:
Member of the European Reference Network for rare, low prevalence and complex diseases of the heart - ERN GUARD-Heart
Molecular Cardiology, ICS Maugeri, IRCCS and Department of Molecular Medicine, University of Pavia, Pavia, Italy
Shimizu W:
Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan
Department of Cardiovascular Medicine, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
Schott JJ:
Member of the European Reference Network for rare, low prevalence and complex diseases of the heart - ERN GUARD-Heart
l'institut du thorax, INSERM, CNRS, Univ Nantes, Nantes, France
l'institut du thorax, CHU Nantes, Service de Cardiologie, Nantes, France
Gourraud JB:
Member of the European Reference Network for rare, low prevalence and complex diseases of the heart - ERN GUARD-Heart
l'institut du thorax, INSERM, CNRS, Univ Nantes, Nantes, France
l'institut du thorax, CHU Nantes, Service de Cardiologie, Nantes, France
Makiyama T:
Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan
Ohno S:
Department of Cardiovascular Medicine, Shiga University of Medical Science, Otsu, Japan
Center for Epidemiologic Research in Asia, Shiga University of Medical Science, Otsu, Japan
Department of Bioscience and Genetics, National Cerebral and Cardiovascular Center, Suita, Japan
Itoh H:
Department of Cardiovascular Medicine, Shiga University of Medical Science, Otsu, Japan
Center for Epidemiologic Research in Asia, Shiga University of Medical Science, Otsu, Japan
Krahn AD:
Heart Rhythm Services, Division of Cardiology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
Antzelevitch C:
Lankenau Institute for Medical Research, Wynnewood, PA
Lankenau Heart Institute, Wynnewood, PA
Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA
Roden DM:
Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN
Department of Medicine, Vanderbilt University Medical Center, Nashville, TN
Department of Pharmacology, Vanderbilt University Medical Center, Nashville, TN
Saenen J:
Department of Cardiology, Antwerp University Hospital, Belgium
Borggrefe M:
Department of Medicine, University Medical Center Mannheim, Mannheim, Germany
German Center for Cardiovascular Research (DZHK), Partner Site Heidelberg/Mannheim, Germany
Odening KE:
Department of Cardiology and Angiology I, Heart Center University of Freiburg, Medical Faculty, Freiburg, Germany
Ellinor PT:
Cardiac Arrhythmia Service, Massachusetts General Hospital, Boston, MA
Cardiovascular Disease Initiative and Program in Medical and Population Genetics, Broad Institute, Cambridge, Boston, MA
Tfelt-Hansen J:
Member of the European Reference Network for rare, low prevalence and complex diseases of the heart - ERN GUARD-Heart
The Department of Cardiology, The Heart Centre, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark
Department of Forensic Medicine, Faculty of Medical Sciences, University of Copenhagen, Copenhagen, Denmark
Skinner JR:
Cardiac Inherited Disease Group, Starship Childrens Hospital, Auckland, New Zealand
van den Berg MP:
Department of cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
Olesen MS:
Laboratory for Molecular Cardiology, Department of Cardiology, The Heart Centre, Rigshospitalet (Copenhagen University Hospital), Copenhagen, Denmark
Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
Brugada-Terradellas J:
Arrhythmia Unit, Hospital Sant Joan de Déu, University of Barcelona, Barcelona,Spain
Cardiovascular Institute, Hospital Clinic de Barcelona, Universitat de Barcelona, Spain
Institut d'Investigació August Pi i Sunyer (IDIBAPS)
Brugada R:
Center for Biomedical Diagnosis, Hospital Clinic de Barcelona, Universitat de Barcelona, Spain. Institut d'Investigació August Pi i Sunyer (IDIBAPS). Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona (Spain). Medical Science Department, School of Medicine, University of Girona, Girona, Spain
Cardiovascular Genetics Center, University of Girona-IDIBGI, Girona, Spain. Medical Science Department, School of Medicine, University of Girona, Girona, Spain
Cardiology Service, Hospital Josep Trueta, Girona, Spain
Makita N:
National Cerebral and Cardiovascular Center Research Institute, Osaka, Japan
Breckpot J:
Member of the European Reference Network for rare, low prevalence and complex diseases of the heart - ERN GUARD-Heart
Centre for human genetics, university hospitals Leuven, Belgium
Yoshinaga M:
National Hospital Organization Kagoshima Medical Center, Japan
Behr ER:
Member of the European Reference Network for rare, low prevalence and complex diseases of the heart - ERN GUARD-Heart
Molecular and Clinical Sciences Research Institute, St George's University of London, London, United Kingdom
Cardiology Clinical Academic Group, St George's University Hospitals NHS Foundation Trust, London, United Kingdom
Rydberg A:
Member of the European Reference Network for rare, low prevalence and complex diseases of the heart - ERN GUARD-Heart
Department of Clinical Sciences, Unit of Paediatrics, Umeå University, Umeå, Sweden
Aiba T:
Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Osaka, Japan
Kääb S:
Department of Internal Medicine I, University Hospital of the Ludwig Maximilians University, Munich, Germany
Priori SG:
Member of the European Reference Network for rare, low prevalence and complex diseases of the heart - ERN GUARD-Heart
Molecular Cardiology, ICS Maugeri, IRCCS and Department of Molecular Medicine, University of Pavia, Pavia, Italy
Guicheney P:
INSERM, Sorbonne University, UMRS 1166, Institute of Cardiometabolism and Nutrition (ICAN), Paris, France
Tan HL:
Amsterdam UMC, University of Amsterdam, Heart Center
Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, Meibergdreef 9, Amsterdam, The Netherlands
Member of the European Reference Network for rare, low prevalence and complex diseases of the heart - ERN GUARD-Heart
Netherlands Heart Institute, Utrecht, The Netherlands
Newton-Cheh C:
Cardiovascular Research Center and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA
Ackerman MJ:
Departments 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
Schwartz PJ:
Member of the European Reference Network for rare, low prevalence and complex diseases of the heart - ERN GUARD-Heart
Istituto Auxologico Italiano, IRCCS, Center for Cardiac Arrhythmias of Genetic Origin, Milan, Italy
Istituto Auxologico Italiano, IRCCS, Laboratory of Cardiovascular Genetics, Milan, Italy
Schulze-Bahr E:
Member of the European Reference Network for rare, low prevalence and complex diseases of the heart - ERN GUARD-Heart
Institute for Genetics of Heart Diseases, Department of Cardiovascular Medicine, University Hospital Muenster, Muenster, Germany
Probst V:
Member of the European Reference Network for rare, low prevalence and complex diseases of the heart - ERN GUARD-Heart
l'institut du thorax, INSERM, CNRS, Univ Nantes, Nantes, France
Department of Cardiovascular Medicine, Graduate School of Medicine, Nippon Medical School, Tokyo, Japan
Horie M:
Department of Cardiovascular Medicine, Shiga University of Medical Science, Otsu, Japan
Center for Epidemiologic Research in Asia, Shiga University of Medical Science, Otsu, Japan
Wilde AA:
Amsterdam UMC, University of Amsterdam, Heart Center
Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, Meibergdreef 9, Amsterdam, The Netherlands
Member of the European Reference Network for rare, low prevalence and complex diseases of the heart - ERN GUARD-Heart
Tanck MWT:
Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Amsterdam UMC, University of Amsterdam. Amsterdam, The Netherlands
Bezzina CR:
Amsterdam UMC, University of Amsterdam, Heart Center
Department of Clinical and Experimental Cardiology, Amsterdam Cardiovascular Sciences, Meibergdreef 9, Amsterdam, The Netherlands
Member of the European Reference Network for rare, low prevalence and complex diseases of the heart - ERN GUARD-Heart
Green Submitted, Green Accepted, Green Published, hybrid
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