title: Common variants at ten loci influence QT interval duration in the QTGEN Study.
abstract: QT interval duration, reflecting myocardial repolarization on the electrocardiogram, is a heritable risk factor for sudden cardiac death and drug-induced arrhythmias. We conducted a meta-analysis of three genome-wide association studies in 13,685 individuals of European ancestry from the Framingham Heart Study, the Rotterdam Study and the Cardiovascular Health Study, as part of the QTGEN consortium. We observed associations at P < 5 x 10(-8) with variants in NOS1AP, KCNQ1, KCNE1, KCNH2 and SCN5A, known to be involved in myocardial repolarization and mendelian long-QT syndromes. Associations were found at five newly identified loci, including 16q21 near NDRG4 and GINS3, 6q22 near PLN, 1p36 near RNF207, 16p13 near LITAF and 17q12 near LIG3 and RFFL. Collectively, the 14 independent variants at these 10 loci explain 5.4-6.5% of the variation in QT interval. These results, together with an accompanying paper, offer insights into myocardial repolarization and suggest candidate genes that could predispose to sudden cardiac death and drug-induced arrhythmias.
authors.affiliation: Center for Human Genetic Research, Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA. cnewtoncheh@chgr.mgh.harvard.edu
authors.forename: Christopher
authors.initials: C
authors.lastname: Newton-Cheh
authors.forename: Mark
authors.initials: M
authors.lastname: Eijgelsheim
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Rice
authors.forename: Paul I W
authors.initials: PI
authors.lastname: de Bakker
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Yin
authors.forename: Karol
authors.initials: K
authors.lastname: Estrada
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Bis
authors.forename: Kristin
authors.initials: K
authors.lastname: Marciante
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivadeneira
authors.forename: Peter A
authors.initials: PA
authors.lastname: Noseworthy
authors.forename: Nona
authors.initials: N
authors.lastname: Sotoodehnia
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Smith
authors.forename: Jerome I
authors.initials: JI
authors.lastname: Rotter
authors.forename: Jan A
authors.initials: JA
authors.lastname: Kors
authors.forename: Jacqueline C M
authors.initials: JC
authors.lastname: Witteman
authors.forename: Albert
authors.initials: A
authors.lastname: Hofman
authors.forename: Susan R
authors.initials: SR
authors.lastname: Heckbert
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: O'Donnell
authors.forename: André G
authors.initials: AG
authors.lastname: Uitterlinden
authors.forename: Bruce M
authors.initials: BM
authors.lastname: Psaty
authors.forename: Thomas
authors.initials: T
authors.lastname: Lumley
authors.forename: Martin G
authors.initials: MG
authors.lastname: Larson
authors.forename: Bruno H Ch
authors.initials: BH
authors.lastname: Stricker
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D000368:Aged; D001145:Arrhythmias, Cardiac / Q000139:chemically induced / Q000235:genetics*; D002874:Chromosome Mapping; D016757:Death, Sudden, Cardiac; D000072237:ERG1 Potassium Channel; D004569:Electroencephalography; D051638:Ether-A-Go-Go Potassium Channels / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation; D015894:Genome, Human; D006801:Humans; D051657:KCNQ1 Potassium Channel / Q000235:genetics; D015201:Meta-Analysis as Topic; D009124:Muscle Proteins / Q000235:genetics; D062554:NAV1.5 Voltage-Gated Sodium Channel; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D024642:Potassium Channels, Voltage-Gated / Q000235:genetics; D012307:Risk Factors; D015222:Sodium Channels / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C489622:KCNE1 protein, human; C000606913:KCNH2 protein, human; D051657:KCNQ1 Potassium Channel; C496909:KCNQ1 protein, human; D009124:Muscle Proteins; D062554:NAV1.5 Voltage-Gated Sodium Channel; C488081:NOS1AP protein, human; D024642:Potassium Channels, Voltage-Gated; C568320:SCN5A protein, human; D015222:Sodium Channels