Evidence map›Paper›PMID 25737393›Full record

ArticleCirculation. Cardiovascular genetics2015

Analysis for Genetic Modifiers of Disease Severity in Patients With Long-QT Syndrome Type 2.

Iris C R M Kolder, Michael W T Tanck, Pieter G Postema, Julien Barc, Moritz F Sinner, Sven Zumhagen, Anja Husemann, Birgit Stallmeyer, Tamara T Koopmann, Nynke Hofman and 12 more

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

Article in Circulation. Cardiovascular genetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.

0numbers the graph read from it
0cells of the map it votes in
28citing papers in PubMed
4.5field-weighted citation impact, top 5% 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

28 citing papers in PubMed, 60 citations in OpenAlex.

  1. Article
  2. Article
  3. 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
  4. Stem cell models of inherited arrhythmias.Nature cardiovascular research · 2024
    Review
  5. Human Genetics of Cardiac Arrhythmias.Advances in experimental medicine and biology · 2024
    Review
  6. Article
  7. Article
  8. Review
  9. Review
  10. Article
  11. Review
  12. Review
  13. Review
  14. The Role of Testosterone and Gonadotropins in Arrhythmogenesis.Journal of the American Heart Association · 2021
    Article
  15. When genetic burden reaches threshold.European heart journal · 2020
    Article
  16. Article
  17. Review
  18. Review
  19. Review
  20. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

22 authors at 4 institutions in 5 countries.

Iris C R M Kolder *Department of Clinical and Experimental Cardiology (I.C.R.M.K., P.G.P., J.B., T.T.K., A.A.M.W., C.R.B.), Department of Clinical Epidemiology, Biostatistics and Bioinformatics (I.C.R.M.K., M.W.T.T.), and Department of Clinical Genetics (N.H.), Academic Medical Center, Amsterdam, the Netherlands; ICIN (Netherlands Heart Institute) (J.B., A.A.M.W., C.R.B.), Utrecht, the Netherlands; Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) 1087, L'Institut du Thorax, Nantes, France (J.B., J.-J.S.); Centre National de la Recherche Scientifique (CNRS) UMR 6291, Nantes, France (J.B., J.-J.S.); Université de Nantes, Nantes, France (J.B., J.-J.S.); Department of Medicine I, University Hospital Munich, Campus Grosshadern and Innenstadt, Ludwig-Maximilians University, Munich, Germany (M.F.S., B.M.B., S.K.); German Center for Cardiovascular Research (DZHK), Munich Heart Alliance, Munich, Germany (S.K.T.M.); Institute for Genetics of Heart Diseases, Department of Cardiovascular Medicine, University Hospital Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Interdisciplinary Centre for Clinical Research (IZKF) of the University of Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Institute of Bioinformatics and Systems Biology (A.P.), and Institute of Human Genetics (A.P., P.L., T.M.), Helmholtz Zentrum München, Neuherberg, Germany; Institute of Human Genetics, Technische Universität München, Munich, Germany (A.P., P.L., T.M.); Department of Medicine (R.J.M., N.H.B.), Department of Molecular and Cellular Pharmacology (R.J.M., N.H.B.), and Hussmann Institute of Human Genomics (R.J.M., N.H.B.), University of Miami Miller School of Medicine, FL; Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN (D.M.R.); Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, Kingdom of Saudi Arabia (A.A.M.W.); and Centre Hospitalier Universitaire (CHU) Nantes, L'Institut du Thorax, Service de Cardiologie, Nantes, France (J.-J.S.).
Michael W T Tanck *Department of Clinical and Experimental Cardiology (I.C.R.M.K., P.G.P., J.B., T.T.K., A.A.M.W., C.R.B.), Department of Clinical Epidemiology, Biostatistics and Bioinformatics (I.C.R.M.K., M.W.T.T.), and Department of Clinical Genetics (N.H.), Academic Medical Center, Amsterdam, the Netherlands; ICIN (Netherlands Heart Institute) (J.B., A.A.M.W., C.R.B.), Utrecht, the Netherlands; Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) 1087, L'Institut du Thorax, Nantes, France (J.B., J.-J.S.); Centre National de la Recherche Scientifique (CNRS) UMR 6291, Nantes, France (J.B., J.-J.S.); Université de Nantes, Nantes, France (J.B., J.-J.S.); Department of Medicine I, University Hospital Munich, Campus Grosshadern and Innenstadt, Ludwig-Maximilians University, Munich, Germany (M.F.S., B.M.B., S.K.); German Center for Cardiovascular Research (DZHK), Munich Heart Alliance, Munich, Germany (S.K.T.M.); Institute for Genetics of Heart Diseases, Department of Cardiovascular Medicine, University Hospital Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Interdisciplinary Centre for Clinical Research (IZKF) of the University of Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Institute of Bioinformatics and Systems Biology (A.P.), and Institute of Human Genetics (A.P., P.L., T.M.), Helmholtz Zentrum München, Neuherberg, Germany; Institute of Human Genetics, Technische Universität München, Munich, Germany (A.P., P.L., T.M.); Department of Medicine (R.J.M., N.H.B.), Department of Molecular and Cellular Pharmacology (R.J.M., N.H.B.), and Hussmann Institute of Human Genomics (R.J.M., N.H.B.), University of Miami Miller School of Medicine, FL; Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN (D.M.R.); Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, Kingdom of Saudi Arabia (A.A.M.W.); and Centre Hospitalier Universitaire (CHU) Nantes, L'Institut du Thorax, Service de Cardiologie, Nantes, France (J.-J.S.).
Pieter G Postema *Department of Clinical and Experimental Cardiology (I.C.R.M.K., P.G.P., J.B., T.T.K., A.A.M.W., C.R.B.), Department of Clinical Epidemiology, Biostatistics and Bioinformatics (I.C.R.M.K., M.W.T.T.), and Department of Clinical Genetics (N.H.), Academic Medical Center, Amsterdam, the Netherlands; ICIN (Netherlands Heart Institute) (J.B., A.A.M.W., C.R.B.), Utrecht, the Netherlands; Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) 1087, L'Institut du Thorax, Nantes, France (J.B., J.-J.S.); Centre National de la Recherche Scientifique (CNRS) UMR 6291, Nantes, France (J.B., J.-J.S.); Université de Nantes, Nantes, France (J.B., J.-J.S.); Department of Medicine I, University Hospital Munich, Campus Grosshadern and Innenstadt, Ludwig-Maximilians University, Munich, Germany (M.F.S., B.M.B., S.K.); German Center for Cardiovascular Research (DZHK), Munich Heart Alliance, Munich, Germany (S.K.T.M.); Institute for Genetics of Heart Diseases, Department of Cardiovascular Medicine, University Hospital Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Interdisciplinary Centre for Clinical Research (IZKF) of the University of Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Institute of Bioinformatics and Systems Biology (A.P.), and Institute of Human Genetics (A.P., P.L., T.M.), Helmholtz Zentrum München, Neuherberg, Germany; Institute of Human Genetics, Technische Universität München, Munich, Germany (A.P., P.L., T.M.); Department of Medicine (R.J.M., N.H.B.), Department of Molecular and Cellular Pharmacology (R.J.M., N.H.B.), and Hussmann Institute of Human Genomics (R.J.M., N.H.B.), University of Miami Miller School of Medicine, FL; Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN (D.M.R.); Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, Kingdom of Saudi Arabia (A.A.M.W.); and Centre Hospitalier Universitaire (CHU) Nantes, L'Institut du Thorax, Service de Cardiologie, Nantes, France (J.-J.S.).
Julien BarcDepartment of Clinical and Experimental Cardiology (I.C.R.M.K., P.G.P., J.B., T.T.K., A.A.M.W., C.R.B.), Department of Clinical Epidemiology, Biostatistics and Bioinformatics (I.C.R.M.K., M.W.T.T.), and Department of Clinical Genetics (N.H.), Academic Medical Center, Amsterdam, the Netherlands; ICIN (Netherlands Heart Institute) (J.B., A.A.M.W., C.R.B.), Utrecht, the Netherlands; Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) 1087, L'Institut du Thorax, Nantes, France (J.B., J.-J.S.); Centre National de la Recherche Scientifique (CNRS) UMR 6291, Nantes, France (J.B., J.-J.S.); Université de Nantes, Nantes, France (J.B., J.-J.S.); Department of Medicine I, University Hospital Munich, Campus Grosshadern and Innenstadt, Ludwig-Maximilians University, Munich, Germany (M.F.S., B.M.B., S.K.); German Center for Cardiovascular Research (DZHK), Munich Heart Alliance, Munich, Germany (S.K.T.M.); Institute for Genetics of Heart Diseases, Department of Cardiovascular Medicine, University Hospital Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Interdisciplinary Centre for Clinical Research (IZKF) of the University of Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Institute of Bioinformatics and Systems Biology (A.P.), and Institute of Human Genetics (A.P., P.L., T.M.), Helmholtz Zentrum München, Neuherberg, Germany; Institute of Human Genetics, Technische Universität München, Munich, Germany (A.P., P.L., T.M.); Department of Medicine (R.J.M., N.H.B.), Department of Molecular and Cellular Pharmacology (R.J.M., N.H.B.), and Hussmann Institute of Human Genomics (R.J.M., N.H.B.), University of Miami Miller School of Medicine, FL; Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN (D.M.R.); Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, Kingdom of Saudi Arabia (A.A.M.W.); and Centre Hospitalier Universitaire (CHU) Nantes, L'Institut du Thorax, Service de Cardiologie, Nantes, France (J.-J.S.).
Moritz F SinnerDepartment of Clinical and Experimental Cardiology (I.C.R.M.K., P.G.P., J.B., T.T.K., A.A.M.W., C.R.B.), Department of Clinical Epidemiology, Biostatistics and Bioinformatics (I.C.R.M.K., M.W.T.T.), and Department of Clinical Genetics (N.H.), Academic Medical Center, Amsterdam, the Netherlands; ICIN (Netherlands Heart Institute) (J.B., A.A.M.W., C.R.B.), Utrecht, the Netherlands; Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) 1087, L'Institut du Thorax, Nantes, France (J.B., J.-J.S.); Centre National de la Recherche Scientifique (CNRS) UMR 6291, Nantes, France (J.B., J.-J.S.); Université de Nantes, Nantes, France (J.B., J.-J.S.); Department of Medicine I, University Hospital Munich, Campus Grosshadern and Innenstadt, Ludwig-Maximilians University, Munich, Germany (M.F.S., B.M.B., S.K.); German Center for Cardiovascular Research (DZHK), Munich Heart Alliance, Munich, Germany (S.K.T.M.); Institute for Genetics of Heart Diseases, Department of Cardiovascular Medicine, University Hospital Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Interdisciplinary Centre for Clinical Research (IZKF) of the University of Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Institute of Bioinformatics and Systems Biology (A.P.), and Institute of Human Genetics (A.P., P.L., T.M.), Helmholtz Zentrum München, Neuherberg, Germany; Institute of Human Genetics, Technische Universität München, Munich, Germany (A.P., P.L., T.M.); Department of Medicine (R.J.M., N.H.B.), Department of Molecular and Cellular Pharmacology (R.J.M., N.H.B.), and Hussmann Institute of Human Genomics (R.J.M., N.H.B.), University of Miami Miller School of Medicine, FL; Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN (D.M.R.); Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, Kingdom of Saudi Arabia (A.A.M.W.); and Centre Hospitalier Universitaire (CHU) Nantes, L'Institut du Thorax, Service de Cardiologie, Nantes, France (J.-J.S.).
Sven ZumhagenDepartment of Clinical and Experimental Cardiology (I.C.R.M.K., P.G.P., J.B., T.T.K., A.A.M.W., C.R.B.), Department of Clinical Epidemiology, Biostatistics and Bioinformatics (I.C.R.M.K., M.W.T.T.), and Department of Clinical Genetics (N.H.), Academic Medical Center, Amsterdam, the Netherlands; ICIN (Netherlands Heart Institute) (J.B., A.A.M.W., C.R.B.), Utrecht, the Netherlands; Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) 1087, L'Institut du Thorax, Nantes, France (J.B., J.-J.S.); Centre National de la Recherche Scientifique (CNRS) UMR 6291, Nantes, France (J.B., J.-J.S.); Université de Nantes, Nantes, France (J.B., J.-J.S.); Department of Medicine I, University Hospital Munich, Campus Grosshadern and Innenstadt, Ludwig-Maximilians University, Munich, Germany (M.F.S., B.M.B., S.K.); German Center for Cardiovascular Research (DZHK), Munich Heart Alliance, Munich, Germany (S.K.T.M.); Institute for Genetics of Heart Diseases, Department of Cardiovascular Medicine, University Hospital Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Interdisciplinary Centre for Clinical Research (IZKF) of the University of Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Institute of Bioinformatics and Systems Biology (A.P.), and Institute of Human Genetics (A.P., P.L., T.M.), Helmholtz Zentrum München, Neuherberg, Germany; Institute of Human Genetics, Technische Universität München, Munich, Germany (A.P., P.L., T.M.); Department of Medicine (R.J.M., N.H.B.), Department of Molecular and Cellular Pharmacology (R.J.M., N.H.B.), and Hussmann Institute of Human Genomics (R.J.M., N.H.B.), University of Miami Miller School of Medicine, FL; Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN (D.M.R.); Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, Kingdom of Saudi Arabia (A.A.M.W.); and Centre Hospitalier Universitaire (CHU) Nantes, L'Institut du Thorax, Service de Cardiologie, Nantes, France (J.-J.S.).
Anja HusemannDepartment of Clinical and Experimental Cardiology (I.C.R.M.K., P.G.P., J.B., T.T.K., A.A.M.W., C.R.B.), Department of Clinical Epidemiology, Biostatistics and Bioinformatics (I.C.R.M.K., M.W.T.T.), and Department of Clinical Genetics (N.H.), Academic Medical Center, Amsterdam, the Netherlands; ICIN (Netherlands Heart Institute) (J.B., A.A.M.W., C.R.B.), Utrecht, the Netherlands; Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) 1087, L'Institut du Thorax, Nantes, France (J.B., J.-J.S.); Centre National de la Recherche Scientifique (CNRS) UMR 6291, Nantes, France (J.B., J.-J.S.); Université de Nantes, Nantes, France (J.B., J.-J.S.); Department of Medicine I, University Hospital Munich, Campus Grosshadern and Innenstadt, Ludwig-Maximilians University, Munich, Germany (M.F.S., B.M.B., S.K.); German Center for Cardiovascular Research (DZHK), Munich Heart Alliance, Munich, Germany (S.K.T.M.); Institute for Genetics of Heart Diseases, Department of Cardiovascular Medicine, University Hospital Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Interdisciplinary Centre for Clinical Research (IZKF) of the University of Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Institute of Bioinformatics and Systems Biology (A.P.), and Institute of Human Genetics (A.P., P.L., T.M.), Helmholtz Zentrum München, Neuherberg, Germany; Institute of Human Genetics, Technische Universität München, Munich, Germany (A.P., P.L., T.M.); Department of Medicine (R.J.M., N.H.B.), Department of Molecular and Cellular Pharmacology (R.J.M., N.H.B.), and Hussmann Institute of Human Genomics (R.J.M., N.H.B.), University of Miami Miller School of Medicine, FL; Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN (D.M.R.); Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, Kingdom of Saudi Arabia (A.A.M.W.); and Centre Hospitalier Universitaire (CHU) Nantes, L'Institut du Thorax, Service de Cardiologie, Nantes, France (J.-J.S.).
Birgit StallmeyerDepartment of Clinical and Experimental Cardiology (I.C.R.M.K., P.G.P., J.B., T.T.K., A.A.M.W., C.R.B.), Department of Clinical Epidemiology, Biostatistics and Bioinformatics (I.C.R.M.K., M.W.T.T.), and Department of Clinical Genetics (N.H.), Academic Medical Center, Amsterdam, the Netherlands; ICIN (Netherlands Heart Institute) (J.B., A.A.M.W., C.R.B.), Utrecht, the Netherlands; Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) 1087, L'Institut du Thorax, Nantes, France (J.B., J.-J.S.); Centre National de la Recherche Scientifique (CNRS) UMR 6291, Nantes, France (J.B., J.-J.S.); Université de Nantes, Nantes, France (J.B., J.-J.S.); Department of Medicine I, University Hospital Munich, Campus Grosshadern and Innenstadt, Ludwig-Maximilians University, Munich, Germany (M.F.S., B.M.B., S.K.); German Center for Cardiovascular Research (DZHK), Munich Heart Alliance, Munich, Germany (S.K.T.M.); Institute for Genetics of Heart Diseases, Department of Cardiovascular Medicine, University Hospital Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Interdisciplinary Centre for Clinical Research (IZKF) of the University of Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Institute of Bioinformatics and Systems Biology (A.P.), and Institute of Human Genetics (A.P., P.L., T.M.), Helmholtz Zentrum München, Neuherberg, Germany; Institute of Human Genetics, Technische Universität München, Munich, Germany (A.P., P.L., T.M.); Department of Medicine (R.J.M., N.H.B.), Department of Molecular and Cellular Pharmacology (R.J.M., N.H.B.), and Hussmann Institute of Human Genomics (R.J.M., N.H.B.), University of Miami Miller School of Medicine, FL; Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN (D.M.R.); Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, Kingdom of Saudi Arabia (A.A.M.W.); and Centre Hospitalier Universitaire (CHU) Nantes, L'Institut du Thorax, Service de Cardiologie, Nantes, France (J.-J.S.).
Tamara T KoopmannDepartment of Clinical and Experimental Cardiology (I.C.R.M.K., P.G.P., J.B., T.T.K., A.A.M.W., C.R.B.), Department of Clinical Epidemiology, Biostatistics and Bioinformatics (I.C.R.M.K., M.W.T.T.), and Department of Clinical Genetics (N.H.), Academic Medical Center, Amsterdam, the Netherlands; ICIN (Netherlands Heart Institute) (J.B., A.A.M.W., C.R.B.), Utrecht, the Netherlands; Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) 1087, L'Institut du Thorax, Nantes, France (J.B., J.-J.S.); Centre National de la Recherche Scientifique (CNRS) UMR 6291, Nantes, France (J.B., J.-J.S.); Université de Nantes, Nantes, France (J.B., J.-J.S.); Department of Medicine I, University Hospital Munich, Campus Grosshadern and Innenstadt, Ludwig-Maximilians University, Munich, Germany (M.F.S., B.M.B., S.K.); German Center for Cardiovascular Research (DZHK), Munich Heart Alliance, Munich, Germany (S.K.T.M.); Institute for Genetics of Heart Diseases, Department of Cardiovascular Medicine, University Hospital Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Interdisciplinary Centre for Clinical Research (IZKF) of the University of Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Institute of Bioinformatics and Systems Biology (A.P.), and Institute of Human Genetics (A.P., P.L., T.M.), Helmholtz Zentrum München, Neuherberg, Germany; Institute of Human Genetics, Technische Universität München, Munich, Germany (A.P., P.L., T.M.); Department of Medicine (R.J.M., N.H.B.), Department of Molecular and Cellular Pharmacology (R.J.M., N.H.B.), and Hussmann Institute of Human Genomics (R.J.M., N.H.B.), University of Miami Miller School of Medicine, FL; Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN (D.M.R.); Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, Kingdom of Saudi Arabia (A.A.M.W.); and Centre Hospitalier Universitaire (CHU) Nantes, L'Institut du Thorax, Service de Cardiologie, Nantes, France (J.-J.S.).
Nynke HofmanDepartment of Clinical and Experimental Cardiology (I.C.R.M.K., P.G.P., J.B., T.T.K., A.A.M.W., C.R.B.), Department of Clinical Epidemiology, Biostatistics and Bioinformatics (I.C.R.M.K., M.W.T.T.), and Department of Clinical Genetics (N.H.), Academic Medical Center, Amsterdam, the Netherlands; ICIN (Netherlands Heart Institute) (J.B., A.A.M.W., C.R.B.), Utrecht, the Netherlands; Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) 1087, L'Institut du Thorax, Nantes, France (J.B., J.-J.S.); Centre National de la Recherche Scientifique (CNRS) UMR 6291, Nantes, France (J.B., J.-J.S.); Université de Nantes, Nantes, France (J.B., J.-J.S.); Department of Medicine I, University Hospital Munich, Campus Grosshadern and Innenstadt, Ludwig-Maximilians University, Munich, Germany (M.F.S., B.M.B., S.K.); German Center for Cardiovascular Research (DZHK), Munich Heart Alliance, Munich, Germany (S.K.T.M.); Institute for Genetics of Heart Diseases, Department of Cardiovascular Medicine, University Hospital Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Interdisciplinary Centre for Clinical Research (IZKF) of the University of Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Institute of Bioinformatics and Systems Biology (A.P.), and Institute of Human Genetics (A.P., P.L., T.M.), Helmholtz Zentrum München, Neuherberg, Germany; Institute of Human Genetics, Technische Universität München, Munich, Germany (A.P., P.L., T.M.); Department of Medicine (R.J.M., N.H.B.), Department of Molecular and Cellular Pharmacology (R.J.M., N.H.B.), and Hussmann Institute of Human Genomics (R.J.M., N.H.B.), University of Miami Miller School of Medicine, FL; Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN (D.M.R.); Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, Kingdom of Saudi Arabia (A.A.M.W.); and Centre Hospitalier Universitaire (CHU) Nantes, L'Institut du Thorax, Service de Cardiologie, Nantes, France (J.-J.S.).
Arne PfeuferDepartment of Clinical and Experimental Cardiology (I.C.R.M.K., P.G.P., J.B., T.T.K., A.A.M.W., C.R.B.), Department of Clinical Epidemiology, Biostatistics and Bioinformatics (I.C.R.M.K., M.W.T.T.), and Department of Clinical Genetics (N.H.), Academic Medical Center, Amsterdam, the Netherlands; ICIN (Netherlands Heart Institute) (J.B., A.A.M.W., C.R.B.), Utrecht, the Netherlands; Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) 1087, L'Institut du Thorax, Nantes, France (J.B., J.-J.S.); Centre National de la Recherche Scientifique (CNRS) UMR 6291, Nantes, France (J.B., J.-J.S.); Université de Nantes, Nantes, France (J.B., J.-J.S.); Department of Medicine I, University Hospital Munich, Campus Grosshadern and Innenstadt, Ludwig-Maximilians University, Munich, Germany (M.F.S., B.M.B., S.K.); German Center for Cardiovascular Research (DZHK), Munich Heart Alliance, Munich, Germany (S.K.T.M.); Institute for Genetics of Heart Diseases, Department of Cardiovascular Medicine, University Hospital Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Interdisciplinary Centre for Clinical Research (IZKF) of the University of Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Institute of Bioinformatics and Systems Biology (A.P.), and Institute of Human Genetics (A.P., P.L., T.M.), Helmholtz Zentrum München, Neuherberg, Germany; Institute of Human Genetics, Technische Universität München, Munich, Germany (A.P., P.L., T.M.); Department of Medicine (R.J.M., N.H.B.), Department of Molecular and Cellular Pharmacology (R.J.M., N.H.B.), and Hussmann Institute of Human Genomics (R.J.M., N.H.B.), University of Miami Miller School of Medicine, FL; Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN (D.M.R.); Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, Kingdom of Saudi Arabia (A.A.M.W.); and Centre Hospitalier Universitaire (CHU) Nantes, L'Institut du Thorax, Service de Cardiologie, Nantes, France (J.-J.S.).
Peter LichtnerDepartment of Clinical and Experimental Cardiology (I.C.R.M.K., P.G.P., J.B., T.T.K., A.A.M.W., C.R.B.), Department of Clinical Epidemiology, Biostatistics and Bioinformatics (I.C.R.M.K., M.W.T.T.), and Department of Clinical Genetics (N.H.), Academic Medical Center, Amsterdam, the Netherlands; ICIN (Netherlands Heart Institute) (J.B., A.A.M.W., C.R.B.), Utrecht, the Netherlands; Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) 1087, L'Institut du Thorax, Nantes, France (J.B., J.-J.S.); Centre National de la Recherche Scientifique (CNRS) UMR 6291, Nantes, France (J.B., J.-J.S.); Université de Nantes, Nantes, France (J.B., J.-J.S.); Department of Medicine I, University Hospital Munich, Campus Grosshadern and Innenstadt, Ludwig-Maximilians University, Munich, Germany (M.F.S., B.M.B., S.K.); German Center for Cardiovascular Research (DZHK), Munich Heart Alliance, Munich, Germany (S.K.T.M.); Institute for Genetics of Heart Diseases, Department of Cardiovascular Medicine, University Hospital Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Interdisciplinary Centre for Clinical Research (IZKF) of the University of Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Institute of Bioinformatics and Systems Biology (A.P.), and Institute of Human Genetics (A.P., P.L., T.M.), Helmholtz Zentrum München, Neuherberg, Germany; Institute of Human Genetics, Technische Universität München, Munich, Germany (A.P., P.L., T.M.); Department of Medicine (R.J.M., N.H.B.), Department of Molecular and Cellular Pharmacology (R.J.M., N.H.B.), and Hussmann Institute of Human Genomics (R.J.M., N.H.B.), University of Miami Miller School of Medicine, FL; Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN (D.M.R.); Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, Kingdom of Saudi Arabia (A.A.M.W.); and Centre Hospitalier Universitaire (CHU) Nantes, L'Institut du Thorax, Service de Cardiologie, Nantes, France (J.-J.S.).
Thomas MeitingerDepartment of Clinical and Experimental Cardiology (I.C.R.M.K., P.G.P., J.B., T.T.K., A.A.M.W., C.R.B.), Department of Clinical Epidemiology, Biostatistics and Bioinformatics (I.C.R.M.K., M.W.T.T.), and Department of Clinical Genetics (N.H.), Academic Medical Center, Amsterdam, the Netherlands; ICIN (Netherlands Heart Institute) (J.B., A.A.M.W., C.R.B.), Utrecht, the Netherlands; Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) 1087, L'Institut du Thorax, Nantes, France (J.B., J.-J.S.); Centre National de la Recherche Scientifique (CNRS) UMR 6291, Nantes, France (J.B., J.-J.S.); Université de Nantes, Nantes, France (J.B., J.-J.S.); Department of Medicine I, University Hospital Munich, Campus Grosshadern and Innenstadt, Ludwig-Maximilians University, Munich, Germany (M.F.S., B.M.B., S.K.); German Center for Cardiovascular Research (DZHK), Munich Heart Alliance, Munich, Germany (S.K.T.M.); Institute for Genetics of Heart Diseases, Department of Cardiovascular Medicine, University Hospital Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Interdisciplinary Centre for Clinical Research (IZKF) of the University of Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Institute of Bioinformatics and Systems Biology (A.P.), and Institute of Human Genetics (A.P., P.L., T.M.), Helmholtz Zentrum München, Neuherberg, Germany; Institute of Human Genetics, Technische Universität München, Munich, Germany (A.P., P.L., T.M.); Department of Medicine (R.J.M., N.H.B.), Department of Molecular and Cellular Pharmacology (R.J.M., N.H.B.), and Hussmann Institute of Human Genomics (R.J.M., N.H.B.), University of Miami Miller School of Medicine, FL; Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN (D.M.R.); Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, Kingdom of Saudi Arabia (A.A.M.W.); and Centre Hospitalier Universitaire (CHU) Nantes, L'Institut du Thorax, Service de Cardiologie, Nantes, France (J.-J.S.).
Britt M BeckmannDepartment of Clinical and Experimental Cardiology (I.C.R.M.K., P.G.P., J.B., T.T.K., A.A.M.W., C.R.B.), Department of Clinical Epidemiology, Biostatistics and Bioinformatics (I.C.R.M.K., M.W.T.T.), and Department of Clinical Genetics (N.H.), Academic Medical Center, Amsterdam, the Netherlands; ICIN (Netherlands Heart Institute) (J.B., A.A.M.W., C.R.B.), Utrecht, the Netherlands; Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) 1087, L'Institut du Thorax, Nantes, France (J.B., J.-J.S.); Centre National de la Recherche Scientifique (CNRS) UMR 6291, Nantes, France (J.B., J.-J.S.); Université de Nantes, Nantes, France (J.B., J.-J.S.); Department of Medicine I, University Hospital Munich, Campus Grosshadern and Innenstadt, Ludwig-Maximilians University, Munich, Germany (M.F.S., B.M.B., S.K.); German Center for Cardiovascular Research (DZHK), Munich Heart Alliance, Munich, Germany (S.K.T.M.); Institute for Genetics of Heart Diseases, Department of Cardiovascular Medicine, University Hospital Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Interdisciplinary Centre for Clinical Research (IZKF) of the University of Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Institute of Bioinformatics and Systems Biology (A.P.), and Institute of Human Genetics (A.P., P.L., T.M.), Helmholtz Zentrum München, Neuherberg, Germany; Institute of Human Genetics, Technische Universität München, Munich, Germany (A.P., P.L., T.M.); Department of Medicine (R.J.M., N.H.B.), Department of Molecular and Cellular Pharmacology (R.J.M., N.H.B.), and Hussmann Institute of Human Genomics (R.J.M., N.H.B.), University of Miami Miller School of Medicine, FL; Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN (D.M.R.); Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, Kingdom of Saudi Arabia (A.A.M.W.); and Centre Hospitalier Universitaire (CHU) Nantes, L'Institut du Thorax, Service de Cardiologie, Nantes, France (J.-J.S.).
Robert J MyerburgDepartment of Clinical and Experimental Cardiology (I.C.R.M.K., P.G.P., J.B., T.T.K., A.A.M.W., C.R.B.), Department of Clinical Epidemiology, Biostatistics and Bioinformatics (I.C.R.M.K., M.W.T.T.), and Department of Clinical Genetics (N.H.), Academic Medical Center, Amsterdam, the Netherlands; ICIN (Netherlands Heart Institute) (J.B., A.A.M.W., C.R.B.), Utrecht, the Netherlands; Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) 1087, L'Institut du Thorax, Nantes, France (J.B., J.-J.S.); Centre National de la Recherche Scientifique (CNRS) UMR 6291, Nantes, France (J.B., J.-J.S.); Université de Nantes, Nantes, France (J.B., J.-J.S.); Department of Medicine I, University Hospital Munich, Campus Grosshadern and Innenstadt, Ludwig-Maximilians University, Munich, Germany (M.F.S., B.M.B., S.K.); German Center for Cardiovascular Research (DZHK), Munich Heart Alliance, Munich, Germany (S.K.T.M.); Institute for Genetics of Heart Diseases, Department of Cardiovascular Medicine, University Hospital Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Interdisciplinary Centre for Clinical Research (IZKF) of the University of Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Institute of Bioinformatics and Systems Biology (A.P.), and Institute of Human Genetics (A.P., P.L., T.M.), Helmholtz Zentrum München, Neuherberg, Germany; Institute of Human Genetics, Technische Universität München, Munich, Germany (A.P., P.L., T.M.); Department of Medicine (R.J.M., N.H.B.), Department of Molecular and Cellular Pharmacology (R.J.M., N.H.B.), and Hussmann Institute of Human Genomics (R.J.M., N.H.B.), University of Miami Miller School of Medicine, FL; Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN (D.M.R.); Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, Kingdom of Saudi Arabia (A.A.M.W.); and Centre Hospitalier Universitaire (CHU) Nantes, L'Institut du Thorax, Service de Cardiologie, Nantes, France (J.-J.S.).
Nanette H BishopricDepartment of Clinical and Experimental Cardiology (I.C.R.M.K., P.G.P., J.B., T.T.K., A.A.M.W., C.R.B.), Department of Clinical Epidemiology, Biostatistics and Bioinformatics (I.C.R.M.K., M.W.T.T.), and Department of Clinical Genetics (N.H.), Academic Medical Center, Amsterdam, the Netherlands; ICIN (Netherlands Heart Institute) (J.B., A.A.M.W., C.R.B.), Utrecht, the Netherlands; Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) 1087, L'Institut du Thorax, Nantes, France (J.B., J.-J.S.); Centre National de la Recherche Scientifique (CNRS) UMR 6291, Nantes, France (J.B., J.-J.S.); Université de Nantes, Nantes, France (J.B., J.-J.S.); Department of Medicine I, University Hospital Munich, Campus Grosshadern and Innenstadt, Ludwig-Maximilians University, Munich, Germany (M.F.S., B.M.B., S.K.); German Center for Cardiovascular Research (DZHK), Munich Heart Alliance, Munich, Germany (S.K.T.M.); Institute for Genetics of Heart Diseases, Department of Cardiovascular Medicine, University Hospital Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Interdisciplinary Centre for Clinical Research (IZKF) of the University of Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Institute of Bioinformatics and Systems Biology (A.P.), and Institute of Human Genetics (A.P., P.L., T.M.), Helmholtz Zentrum München, Neuherberg, Germany; Institute of Human Genetics, Technische Universität München, Munich, Germany (A.P., P.L., T.M.); Department of Medicine (R.J.M., N.H.B.), Department of Molecular and Cellular Pharmacology (R.J.M., N.H.B.), and Hussmann Institute of Human Genomics (R.J.M., N.H.B.), University of Miami Miller School of Medicine, FL; Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN (D.M.R.); Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, Kingdom of Saudi Arabia (A.A.M.W.); and Centre Hospitalier Universitaire (CHU) Nantes, L'Institut du Thorax, Service de Cardiologie, Nantes, France (J.-J.S.).
Dan M RodenDepartment of Clinical and Experimental Cardiology (I.C.R.M.K., P.G.P., J.B., T.T.K., A.A.M.W., C.R.B.), Department of Clinical Epidemiology, Biostatistics and Bioinformatics (I.C.R.M.K., M.W.T.T.), and Department of Clinical Genetics (N.H.), Academic Medical Center, Amsterdam, the Netherlands; ICIN (Netherlands Heart Institute) (J.B., A.A.M.W., C.R.B.), Utrecht, the Netherlands; Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) 1087, L'Institut du Thorax, Nantes, France (J.B., J.-J.S.); Centre National de la Recherche Scientifique (CNRS) UMR 6291, Nantes, France (J.B., J.-J.S.); Université de Nantes, Nantes, France (J.B., J.-J.S.); Department of Medicine I, University Hospital Munich, Campus Grosshadern and Innenstadt, Ludwig-Maximilians University, Munich, Germany (M.F.S., B.M.B., S.K.); German Center for Cardiovascular Research (DZHK), Munich Heart Alliance, Munich, Germany (S.K.T.M.); Institute for Genetics of Heart Diseases, Department of Cardiovascular Medicine, University Hospital Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Interdisciplinary Centre for Clinical Research (IZKF) of the University of Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Institute of Bioinformatics and Systems Biology (A.P.), and Institute of Human Genetics (A.P., P.L., T.M.), Helmholtz Zentrum München, Neuherberg, Germany; Institute of Human Genetics, Technische Universität München, Munich, Germany (A.P., P.L., T.M.); Department of Medicine (R.J.M., N.H.B.), Department of Molecular and Cellular Pharmacology (R.J.M., N.H.B.), and Hussmann Institute of Human Genomics (R.J.M., N.H.B.), University of Miami Miller School of Medicine, FL; Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN (D.M.R.); Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, Kingdom of Saudi Arabia (A.A.M.W.); and Centre Hospitalier Universitaire (CHU) Nantes, L'Institut du Thorax, Service de Cardiologie, Nantes, France (J.-J.S.).
Stefan KääbDepartment of Clinical and Experimental Cardiology (I.C.R.M.K., P.G.P., J.B., T.T.K., A.A.M.W., C.R.B.), Department of Clinical Epidemiology, Biostatistics and Bioinformatics (I.C.R.M.K., M.W.T.T.), and Department of Clinical Genetics (N.H.), Academic Medical Center, Amsterdam, the Netherlands; ICIN (Netherlands Heart Institute) (J.B., A.A.M.W., C.R.B.), Utrecht, the Netherlands; Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) 1087, L'Institut du Thorax, Nantes, France (J.B., J.-J.S.); Centre National de la Recherche Scientifique (CNRS) UMR 6291, Nantes, France (J.B., J.-J.S.); Université de Nantes, Nantes, France (J.B., J.-J.S.); Department of Medicine I, University Hospital Munich, Campus Grosshadern and Innenstadt, Ludwig-Maximilians University, Munich, Germany (M.F.S., B.M.B., S.K.); German Center for Cardiovascular Research (DZHK), Munich Heart Alliance, Munich, Germany (S.K.T.M.); Institute for Genetics of Heart Diseases, Department of Cardiovascular Medicine, University Hospital Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Interdisciplinary Centre for Clinical Research (IZKF) of the University of Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Institute of Bioinformatics and Systems Biology (A.P.), and Institute of Human Genetics (A.P., P.L., T.M.), Helmholtz Zentrum München, Neuherberg, Germany; Institute of Human Genetics, Technische Universität München, Munich, Germany (A.P., P.L., T.M.); Department of Medicine (R.J.M., N.H.B.), Department of Molecular and Cellular Pharmacology (R.J.M., N.H.B.), and Hussmann Institute of Human Genomics (R.J.M., N.H.B.), University of Miami Miller School of Medicine, FL; Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN (D.M.R.); Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, Kingdom of Saudi Arabia (A.A.M.W.); and Centre Hospitalier Universitaire (CHU) Nantes, L'Institut du Thorax, Service de Cardiologie, Nantes, France (J.-J.S.).
Arthur A M WildeDepartment of Clinical and Experimental Cardiology (I.C.R.M.K., P.G.P., J.B., T.T.K., A.A.M.W., C.R.B.), Department of Clinical Epidemiology, Biostatistics and Bioinformatics (I.C.R.M.K., M.W.T.T.), and Department of Clinical Genetics (N.H.), Academic Medical Center, Amsterdam, the Netherlands; ICIN (Netherlands Heart Institute) (J.B., A.A.M.W., C.R.B.), Utrecht, the Netherlands; Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) 1087, L'Institut du Thorax, Nantes, France (J.B., J.-J.S.); Centre National de la Recherche Scientifique (CNRS) UMR 6291, Nantes, France (J.B., J.-J.S.); Université de Nantes, Nantes, France (J.B., J.-J.S.); Department of Medicine I, University Hospital Munich, Campus Grosshadern and Innenstadt, Ludwig-Maximilians University, Munich, Germany (M.F.S., B.M.B., S.K.); German Center for Cardiovascular Research (DZHK), Munich Heart Alliance, Munich, Germany (S.K.T.M.); Institute for Genetics of Heart Diseases, Department of Cardiovascular Medicine, University Hospital Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Interdisciplinary Centre for Clinical Research (IZKF) of the University of Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Institute of Bioinformatics and Systems Biology (A.P.), and Institute of Human Genetics (A.P., P.L., T.M.), Helmholtz Zentrum München, Neuherberg, Germany; Institute of Human Genetics, Technische Universität München, Munich, Germany (A.P., P.L., T.M.); Department of Medicine (R.J.M., N.H.B.), Department of Molecular and Cellular Pharmacology (R.J.M., N.H.B.), and Hussmann Institute of Human Genomics (R.J.M., N.H.B.), University of Miami Miller School of Medicine, FL; Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN (D.M.R.); Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, Kingdom of Saudi Arabia (A.A.M.W.); and Centre Hospitalier Universitaire (CHU) Nantes, L'Institut du Thorax, Service de Cardiologie, Nantes, France (J.-J.S.).
Jean-Jacques Schott *Department of Clinical and Experimental Cardiology (I.C.R.M.K., P.G.P., J.B., T.T.K., A.A.M.W., C.R.B.), Department of Clinical Epidemiology, Biostatistics and Bioinformatics (I.C.R.M.K., M.W.T.T.), and Department of Clinical Genetics (N.H.), Academic Medical Center, Amsterdam, the Netherlands; ICIN (Netherlands Heart Institute) (J.B., A.A.M.W., C.R.B.), Utrecht, the Netherlands; Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) 1087, L'Institut du Thorax, Nantes, France (J.B., J.-J.S.); Centre National de la Recherche Scientifique (CNRS) UMR 6291, Nantes, France (J.B., J.-J.S.); Université de Nantes, Nantes, France (J.B., J.-J.S.); Department of Medicine I, University Hospital Munich, Campus Grosshadern and Innenstadt, Ludwig-Maximilians University, Munich, Germany (M.F.S., B.M.B., S.K.); German Center for Cardiovascular Research (DZHK), Munich Heart Alliance, Munich, Germany (S.K.T.M.); Institute for Genetics of Heart Diseases, Department of Cardiovascular Medicine, University Hospital Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Interdisciplinary Centre for Clinical Research (IZKF) of the University of Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Institute of Bioinformatics and Systems Biology (A.P.), and Institute of Human Genetics (A.P., P.L., T.M.), Helmholtz Zentrum München, Neuherberg, Germany; Institute of Human Genetics, Technische Universität München, Munich, Germany (A.P., P.L., T.M.); Department of Medicine (R.J.M., N.H.B.), Department of Molecular and Cellular Pharmacology (R.J.M., N.H.B.), and Hussmann Institute of Human Genomics (R.J.M., N.H.B.), University of Miami Miller School of Medicine, FL; Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN (D.M.R.); Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, Kingdom of Saudi Arabia (A.A.M.W.); and Centre Hospitalier Universitaire (CHU) Nantes, L'Institut du Thorax, Service de Cardiologie, Nantes, France (J.-J.S.).
Eric Schulze-Bahr *Department of Clinical and Experimental Cardiology (I.C.R.M.K., P.G.P., J.B., T.T.K., A.A.M.W., C.R.B.), Department of Clinical Epidemiology, Biostatistics and Bioinformatics (I.C.R.M.K., M.W.T.T.), and Department of Clinical Genetics (N.H.), Academic Medical Center, Amsterdam, the Netherlands; ICIN (Netherlands Heart Institute) (J.B., A.A.M.W., C.R.B.), Utrecht, the Netherlands; Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) 1087, L'Institut du Thorax, Nantes, France (J.B., J.-J.S.); Centre National de la Recherche Scientifique (CNRS) UMR 6291, Nantes, France (J.B., J.-J.S.); Université de Nantes, Nantes, France (J.B., J.-J.S.); Department of Medicine I, University Hospital Munich, Campus Grosshadern and Innenstadt, Ludwig-Maximilians University, Munich, Germany (M.F.S., B.M.B., S.K.); German Center for Cardiovascular Research (DZHK), Munich Heart Alliance, Munich, Germany (S.K.T.M.); Institute for Genetics of Heart Diseases, Department of Cardiovascular Medicine, University Hospital Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Interdisciplinary Centre for Clinical Research (IZKF) of the University of Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Institute of Bioinformatics and Systems Biology (A.P.), and Institute of Human Genetics (A.P., P.L., T.M.), Helmholtz Zentrum München, Neuherberg, Germany; Institute of Human Genetics, Technische Universität München, Munich, Germany (A.P., P.L., T.M.); Department of Medicine (R.J.M., N.H.B.), Department of Molecular and Cellular Pharmacology (R.J.M., N.H.B.), and Hussmann Institute of Human Genomics (R.J.M., N.H.B.), University of Miami Miller School of Medicine, FL; Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN (D.M.R.); Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, Kingdom of Saudi Arabia (A.A.M.W.); and Centre Hospitalier Universitaire (CHU) Nantes, L'Institut du Thorax, Service de Cardiologie, Nantes, France (J.-J.S.).
Connie R Bezzina *Department of Clinical and Experimental Cardiology (I.C.R.M.K., P.G.P., J.B., T.T.K., A.A.M.W., C.R.B.), Department of Clinical Epidemiology, Biostatistics and Bioinformatics (I.C.R.M.K., M.W.T.T.), and Department of Clinical Genetics (N.H.), Academic Medical Center, Amsterdam, the Netherlands; ICIN (Netherlands Heart Institute) (J.B., A.A.M.W., C.R.B.), Utrecht, the Netherlands; Institut National de la Santé et de la Recherche Médicale (INSERM) Unité Mixte de Recherche (UMR) 1087, L'Institut du Thorax, Nantes, France (J.B., J.-J.S.); Centre National de la Recherche Scientifique (CNRS) UMR 6291, Nantes, France (J.B., J.-J.S.); Université de Nantes, Nantes, France (J.B., J.-J.S.); Department of Medicine I, University Hospital Munich, Campus Grosshadern and Innenstadt, Ludwig-Maximilians University, Munich, Germany (M.F.S., B.M.B., S.K.); German Center for Cardiovascular Research (DZHK), Munich Heart Alliance, Munich, Germany (S.K.T.M.); Institute for Genetics of Heart Diseases, Department of Cardiovascular Medicine, University Hospital Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Interdisciplinary Centre for Clinical Research (IZKF) of the University of Münster, Münster, Germany (S.Z., A.H., B.S., E.S.-B.); Institute of Bioinformatics and Systems Biology (A.P.), and Institute of Human Genetics (A.P., P.L., T.M.), Helmholtz Zentrum München, Neuherberg, Germany; Institute of Human Genetics, Technische Universität München, Munich, Germany (A.P., P.L., T.M.); Department of Medicine (R.J.M., N.H.B.), Department of Molecular and Cellular Pharmacology (R.J.M., N.H.B.), and Hussmann Institute of Human Genomics (R.J.M., N.H.B.), University of Miami Miller School of Medicine, FL; Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN (D.M.R.); Princess Al-Jawhara Al-Brahim Centre of Excellence in Research of Hereditary Disorders, Jeddah, Kingdom of Saudi Arabia (A.A.M.W.); and Centre Hospitalier Universitaire (CHU) Nantes, L'Institut du Thorax, Service de Cardiologie, Nantes, France (J.-J.S.).
Netherlands Heart Institute · NLInserm · FRCentre National de la Recherche Scientifique · FRLudwig-Maximilians-Universität München · DE

Funding

Transcription Programming in Cardiac GrowthR01HL071094 · NHLBI · UNIVERSITY OF MIAMI SCHOOL OF MEDICINE · PI BISHOPRIC, NANETTE HAHR · 2003 to 2012
$3.4M
NHLBI NIH HHS R01 HL071094
6 · The paper itself

Abstract

backgroundConsiderable interest exists in the identification of genetic modifiers of disease severity in the long-QT syndrome (LQTS) as their identification may contribute to refinement of risk stratification. METHODS AND

resultsWe searched for single-nucleotide polymorphisms (SNPs) that modulate the corrected QT (QTc)-interval and the occurrence of cardiac events in 639 patients harboring different mutations in KCNH2. We analyzed 1201 SNPs in and around 18 candidate genes, and in another approach investigated 22 independent SNPs previously identified as modulators of QTc-interval in genome-wide association studies in the general population. In an analysis for quantitative effects on the QTc-interval, 3 independent SNPs at NOS1AP (rs10494366, P=9.5×10(-8); rs12143842, P=4.8×10(-7); and rs2880058, P=8.6×10(-7)) were strongly associated with the QTc-interval with marked effects (>12 ms/allele). Analysis of patients versus general population controls uncovered enrichment of QTc-prolonging alleles in patients for 2 SNPs, located respectively at NOS1AP (rs12029454; odds ratio, 1.85; 95% confidence interval, 1.32-2.59; P=3×10(-4)) and KCNQ1 (rs12576239; odds ratio, 1.84; 95% confidence interval, 1.31-2.60; P=5×10(-4)). An analysis of the cumulative effect of the 6 NOS1AP SNPs by means of a multilocus genetic risk score (GRS(NOS1AP)) uncovered a strong linear relationship between GRS(NOS1AP) and the QTc-interval (P=4.2×10(-7)). Furthermore, patients with a GRS(NOS1AP) in the lowest quartile had a lower relative risk of cardiac events compared with patients in the other quartiles combined (P=0.039).

conclusionsWe uncovered unexpectedly large effects of NOS1AP SNPs on the QTc-interval and a trend for effects on risk of cardiac events. For the first time, we linked common genetic variation at KCNQ1 with risk of long-QT syndrome.

Indexed as

Adaptor Proteins, Signal TransducingAdrenergic beta-AntagonistsAllelesCase-Control StudiesElectrocardiographyFemaleGenome-Wide Association StudyGenotypeHumansKCNQ1 Potassium ChannelLong QT SyndromeMaleOdds RatioPolymorphism, Single NucleotideRisk FactorsSeverity of Illness IndexAdaptor Proteins, Signal TransducingAdrenergic beta-AntagonistsKCNQ1 Potassium ChannelKCNQ1 protein, humanNOS1AP protein, humanarrhythmias, cardiacion channelslong-QT syndrome

Identifiers

PMID25737393
PMCPMC4770255
OpenAlexW2157436620

What OpenQuestion holds

Textmetadata
LicenceTDM
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.