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Common variants at ten loci modulate the QT interval duration in the QTSCD Study

Contributeurs/tricesEhret, Georg Benedikt
Publié dansNature genetics, vol. 41, no. 4, p. 407-414
Date de publication2009
Résumé

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.

Mots-clés
  • Arrhythmias, Cardiac/*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
  • Potassium Channels, Inwardly Rectifying/genetics
  • Reproducibility of Results
  • Sodium Channels/genetics
Citation (format ISO)
EHRET, Georg Benedikt. Common variants at ten loci modulate the QT interval duration in the QTSCD Study. In: Nature genetics, 2009, vol. 41, n° 4, p. 407–414. doi: 10.1038/ng.362
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ISSN du journal1061-4036
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