title: A common variant near the KCNJ2 gene is associated with T-peak to T-end interval.
abstract: BACKGROUND
  T-peak to T-end (TPE) interval on the electrocardiogram is a measure of myocardial dispersion of repolarization and is associated with an increased risk of ventricular arrhythmias. The genetic factors affecting the TPE interval are largely unknown.
  
  
  OBJECTIVE
  To identify common genetic variants that affect the duration of the TPE interval in the general population.
  
  
  METHODS
  We performed a genome-wide association study on 1870 individuals of Finnish origin participating in the Health 2000 Study. The TPE interval was measured from T-peak to T-wave end in leads II, V(2), and V(5) on resting electrocardiograms, and the mean of these TPE intervals was adjusted for age, sex, and Cornell voltage-duration product. We sought replication for a genome-wide significant result in the 3745 subjects from the Framingham Heart Study.
  
  
  RESULTS
  We identified a locus on 17q24 that was associated with the TPE interval. The minor allele of the common variant rs7219669 was associated with a 1.8-ms shortening of the TPE interval (P = 1.1 × 10(-10)). The association was replicated in the Framingham Heart Study (-1.5 ms; P = 1.3 × 10(-4)). The overall effect estimate of rs7219669 in the 2 studies was -1.7 ms (P = 5.7 × 10(-14)). The common variant rs7219669 maps downstream of the KCNJ2 gene, in which rare mutations cause congenital long and short QT syndromes.
  
  
  CONCLUSIONS
  The common variant rs7219669 is associated with the TPE interval and is thus a candidate to modify repolarization-related arrhythmia susceptibility in individuals carrying the major allele of this polymorphism.
authors.affiliation: Research Program in Molecular Medicine, University of Helsinki, Helsinki, Finland. Annukka.Marjamaa@helsinki.fi
authors.forename: Annukka
authors.initials: A
authors.lastname: Marjamaa
authors.forename: Lasse
authors.initials: L
authors.lastname: Oikarinen
authors.forename: Kimmo
authors.initials: K
authors.lastname: Porthan
authors.forename: Samuli
authors.initials: S
authors.lastname: Ripatti
authors.forename: Gina
authors.initials: G
authors.lastname: Peloso
authors.forename: Peter A
authors.initials: PA
authors.lastname: Noseworthy
authors.forename: Matti
authors.initials: M
authors.lastname: Viitasalo
authors.forename: Markku S
authors.initials: MS
authors.lastname: Nieminen
authors.forename: Lauri
authors.initials: L
authors.lastname: Toivonen
authors.forename: Kimmo
authors.initials: K
authors.lastname: Kontula
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Aki S
authors.initials: AS
authors.lastname: Havulinna
authors.forename: Antti
authors.initials: A
authors.lastname: Jula
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: O'Donnell
authors.forename: Christopher
authors.initials: C
authors.lastname: Newton-Cheh
authors.forename: Markus
authors.initials: M
authors.lastname: Perola
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D019175:DNA Methylation; D004562:Electrocardiography; D022062:Electrophysiologic Techniques, Cardiac; D005260:Female; D005387:Finland; D020862:GC Rich Sequence / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D055106:Genome-Wide Association Study; D006329:Heart Conduction System / Q000503:physiopathology*; D006801:Humans; D008133:Long QT Syndrome / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*
chemical_list: C489457:KCNJ2 protein, human; D024661:Potassium Channels, Inwardly Rectifying