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

Nat Genet. 2009 Apr;41(4):407-14. doi: 10.1038/ng.362. Epub 2009 Mar 22.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arrhythmias, Cardiac / genetics*
  • Chromosome Mapping
  • ERG1 Potassium Channel
  • Electrocardiography
  • Electrophysiology / methods
  • Ether-A-Go-Go Potassium Channels / genetics
  • Genetic Variation*
  • Heart / physiology
  • Heart / physiopathology
  • Humans
  • Ion Channels / genetics*
  • KCNQ1 Potassium Channel / genetics
  • Long QT Syndrome / genetics*
  • Muscle Proteins / genetics
  • NAV1.5 Voltage-Gated Sodium Channel
  • Potassium Channels, Inwardly Rectifying / genetics
  • Reproducibility of Results
  • Sodium Channels / genetics

Substances

  • ERG1 Potassium Channel
  • Ether-A-Go-Go Potassium Channels
  • Ion Channels
  • KCNH2 protein, human
  • KCNJ2 protein, human
  • KCNQ1 Potassium Channel
  • KCNQ1 protein, human
  • Muscle Proteins
  • NAV1.5 Voltage-Gated Sodium Channel
  • Potassium Channels, Inwardly Rectifying
  • SCN5A protein, human
  • Sodium Channels