title: Common variants at ten loci modulate the QT interval duration in the QTSCD Study.
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.
authors.affiliation: Institute of Human Genetics, Helmholtz Center Munich, Germany. arne.pfeufer@helmholtz-muenchen.de
authors.forename: Arne
authors.initials: A
authors.lastname: Pfeufer
authors.forename: Serena
authors.initials: S
authors.lastname: Sanna
authors.forename: Dan E
authors.initials: DE
authors.lastname: Arking
authors.forename: Martina
authors.initials: M
authors.lastname: Müller
authors.forename: Vesela
authors.initials: V
authors.lastname: Gateva
authors.forename: Christian
authors.initials: C
authors.lastname: Fuchsberger
authors.forename: Georg B
authors.initials: GB
authors.lastname: Ehret
authors.forename: Marco
authors.initials: M
authors.lastname: Orrú
authors.forename: Cristian
authors.initials: C
authors.lastname: Pattaro
authors.forename: Anna
authors.initials: A
authors.lastname: Köttgen
authors.forename: Siegfried
authors.initials: S
authors.lastname: Perz
authors.forename: Gianluca
authors.initials: G
authors.lastname: Usala
authors.forename: Maja
authors.initials: M
authors.lastname: Barbalic
authors.forename: Man
authors.initials: M
authors.lastname: Li
authors.forename: Benno
authors.initials: B
authors.lastname: Pütz
authors.forename: Angelo
authors.initials: A
authors.lastname: Scuteri
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Prineas
authors.forename: Moritz F
authors.initials: MF
authors.lastname: Sinner
authors.forename: Christian
authors.initials: C
authors.lastname: Gieger
authors.forename: Samer S
authors.initials: SS
authors.lastname: Najjar
authors.forename: W H Linda
authors.initials: WH
authors.lastname: Kao
authors.forename: Thomas W
authors.initials: TW
authors.lastname: Mühleisen
authors.forename: Mariano
authors.initials: M
authors.lastname: Dei
authors.forename: Christine
authors.initials: C
authors.lastname: Happle
authors.forename: Stefan
authors.initials: S
authors.lastname: Möhlenkamp
authors.forename: Laura
authors.initials: L
authors.lastname: Crisponi
authors.forename: Raimund
authors.initials: R
authors.lastname: Erbel
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Jöckel
authors.forename: Silvia
authors.initials: S
authors.lastname: Naitza
authors.forename: Gerhard
authors.initials: G
authors.lastname: Steinbeck
authors.forename: Fabio
authors.initials: F
authors.lastname: Marroni
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Hicks
authors.forename: Edward
authors.initials: E
authors.lastname: Lakatta
authors.forename: Bertram
authors.initials: B
authors.lastname: Müller-Myhsok
authors.forename: Peter P
authors.initials: PP
authors.lastname: Pramstaller
authors.forename: H-Erich
authors.initials: HE
authors.lastname: Wichmann
authors.forename: David
authors.initials: D
authors.lastname: Schlessinger
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
authors.forename: Thomas
authors.initials: T
authors.lastname: Meitinger
authors.forename: Manuela
authors.initials: M
authors.lastname: Uda
authors.forename: Josef
authors.initials: J
authors.lastname: Coresh
authors.forename: Stefan
authors.initials: S
authors.lastname: Kääb
authors.forename: Gonçalo R
authors.initials: GR
authors.lastname: Abecasis
authors.forename: Aravinda
authors.initials: A
authors.lastname: Chakravarti
mesh_terms: D001145:Arrhythmias, Cardiac / Q000235:genetics*; D002874:Chromosome Mapping; D000072237:ERG1 Potassium Channel; D004562:Electrocardiography; D004594:Electrophysiology / Q000379:methods; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics; D014644:Genetic Variation; D006321:Heart / Q000502:physiology / Q000503:physiopathology; D006801:Humans; D007473:Ion Channels / Q000235:genetics*; D051657:KCNQ1 Potassium Channel / Q000235:genetics; D008133:Long QT Syndrome / Q000235:genetics*; D009124:Muscle Proteins / Q000235:genetics; D062554:NAV1.5 Voltage-Gated Sodium Channel; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D015203:Reproducibility of Results; D015222:Sodium Channels / Q000235:genetics
chemical_list: D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D007473:Ion Channels; C000606913:KCNH2 protein, human; C489457:KCNJ2 protein, human; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; D024661:Potassium Channels, Inwardly Rectifying; C568320:SCN5A protein, human; D015222:Sodium Channels