1. Common variants at ten loci modulate the QT interval duration in the QTSCD Study
- Author
-
Thomas W. Mühleisen, K. H. Jöckel, Peter P. Pramstaller, Thomas Meitinger, Aravinda Chakravarti, Silvia Naitza, Christine Happle, Christian Gieger, Mariano Dei, Ronald J. Prineas, Andrew A. Hicks, Maja Barbalić, Laura Crisponi, Georg B. Ehret, Man Li, Moritz F. Sinner, Benno Pütz, Siegfried Perz, Raimund Erbel, Cristian Pattaro, Eric Boerwinkle, Marco Orr, Manuela Uda, Martina Müller, Gianluca Usala, Gerhard Steinbeck, Samer S. Najjar, Dan E. Arking, Fabio Marroni, Serena Sanna, Stefan Möhlenkamp, Anna Köttgen, Christian Fuchsberger, Arne Pfeufer, Stefan Kääb, David Schlessinger, Josef Coresh, Edward G. Lakatta, H.-Erich Wichmann, W. H. Linda Kao, Angelo Scuteri, Bertram Müller-Myhsok, Gonçalo R. Abecasis, and Vesela Gateva
- Subjects
Candidate gene ,Potassium Channels ,Sodium Channels/genetics ,Muscle Proteins ,Arrhythmias ,Ion Channels ,Sodium Channels ,NAV1.5 Voltage-Gated Sodium Channel ,Sudden cardiac death ,Ether-A-Go-Go Potassium Channels/genetics ,Electrocardiography ,Arrhythmias, Cardiac/*genetics ,ddc:616 ,Muscle Proteins/genetics ,Genetics ,education.field_of_study ,Cardiac electrophysiology ,Chromosome Mapping ,Heart ,Genetic Variation ,Inwardly Rectifying ,Electrophysiology ,Electrophysiology/methods ,Long QT Syndrome ,KCNQ1 Potassium Channel ,cardiovascular system ,Cardiac ,Long QT syndrome ,Population ,genetics, Chromosome Mapping, Electrocardiography, Electrophysiology ,methods, Ether-A-Go-Go Potassium Channels ,genetics, Genetic Variation, Heart ,physiology/physiopathology, Humans, Ion Channels ,genetics, KCNQ1 Potassium Channel ,genetics, Long QT Syndrome ,genetics, Muscle Proteins ,genetics, NAV1.5 Voltage-Gated Sodium Channel, Potassium Channels ,genetics, Reproducibility of Results, Sodium Channels ,genetics ,Locus (genetics) ,Biology ,QT interval ,methods ,medicine ,Humans ,Repolarization ,cardiovascular diseases ,education ,Reproducibility of Results ,physiology/physiopathology ,medicine.disease ,Ether-A-Go-Go Potassium Channels ,Long QT Syndrome/*genetics ,Ion Channels/*genetics ,Heart/physiology/physiopathology ,Potassium Channels, Inwardly Rectifying/genetics ,KCNQ1 Potassium Channel/genetics - Abstract
The QT interval, a measure of cardiac repolarization, predisposes to ventricular arrhythmias and sudden cardiac death (SCD) when prolonged or shortened. A common variant in NOS1AP is known to influence repolarization. We analyze genome-wide data from five population-based cohorts (ARIC, KORA, SardiNIA, GenNOVA and HNR) with a total of 15, 842 individuals of European ancestry, to confirm the NOS1AP association and identify nine additional loci at P < 5 x 10(-8). Four loci map near the monogenic long-QT syndrome genes KCNQ1, KCNH2, SCN5A and KCNJ2. Two other loci include ATP1B1 and PLN, genes with established electrophysiological function, whereas three map to RNF207, near LITAF and within NDRG4-GINS3-SETD6-CNOT1, respectively, all of which have not previously been implicated in cardiac electrophysiology. These results, together with an accompanying paper from the QTGEN consortium, identify new candidate genes for ventricular arrhythmias and SCD.
- Published
- 2009