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


RESULTS
We 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).


CONCLUSIONS
We 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.
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.).
Iris C R M
ICRM
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
MWT
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
PG
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
J
Barc
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.).
Moritz F
MF
Sinner
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.).
Sven
S
Zumhagen
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.).
Anja
A
Husemann
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.).
Birgit
B
Stallmeyer
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.).
Tamara T
TT
Koopmann
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.).
Nynke
N
Hofman
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.).
Arne
A
Pfeufer
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.).
Peter
P
Lichtner
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.).
Thomas
T
Meitinger
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.).
Britt M
BM
Beckmann
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.).
Robert J
RJ
Myerburg
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.).
Nanette H
NH
Bishopric
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.).
Dan M
DM
Roden
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.).
Stefan
S
Kääb
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.).
Arthur A M
AAM
Wilde
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.).
Jean-Jacques
JJ
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
E
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
CR
Bezzina
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000319:Adrenergic beta-Antagonists / Q000627:therapeutic use; D000483:Alleles; D016022:Case-Control Studies; D004562:Electrocardiography; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics; D008133:Long QT Syndrome / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D008297:Male; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012720:Severity of Illness Index
D048868:Adaptor Proteins, Signal Transducing; D000319:Adrenergic beta-Antagonists; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; C488081:NOS1AP protein, human
arrhythmias, cardiac; ion channels; long-QT syndrome