03137nas a2200673 4500008004100000022001400041245008300055210006900138260001300207300001200220490000700232520108000239653004101319653001001360653000901370653002501379653002301404653002701427653002701454653002701481653003701508653004001545653003801585653002201623653001801645653001101663653002801674653002701702653002001729653004001749653003601789653003801825653001701863653002001880100002901900700002201929700002101951700002501972700001701997700001902014700001902033700002302052700002602075700002502101700002202126700002302148700002202171700001702193700003002210700001902240700002302259700003002282700002802312700002002340700001902360700002202379700002602401856003602427 2009 eng d a1546-171800aCommon variants at ten loci influence QT interval duration in the QTGEN Study.0 aCommon variants at ten loci influence QT interval duration in th c2009 Apr a399-4060 v413 a
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.
10aAdaptor Proteins, Signal Transducing10aAdult10aAged10aArrhythmias, Cardiac10aChromosome Mapping10aDeath, Sudden, Cardiac10aElectroencephalography10aERG1 Potassium Channel10aEther-A-Go-Go Potassium Channels10aEuropean Continental Ancestry Group10aGenetic Predisposition to Disease10aGenetic Variation10aGenome, Human10aHumans10aKCNQ1 Potassium Channel10aMeta-Analysis as Topic10aMuscle Proteins10aNAV1.5 Voltage-Gated Sodium Channel10aPolymorphism, Single Nucleotide10aPotassium Channels, Voltage-Gated10aRisk Factors10aSodium Channels1 aNewton-Cheh, Christopher1 aEijgelsheim, Mark1 aRice, Kenneth, M1 ade Bakker, Paul, I W1 aYin, Xiaoyan1 aEstrada, Karol1 aBis, Joshua, C1 aMarciante, Kristin1 aRivadeneira, Fernando1 aNoseworthy, Peter, A1 aSotoodehnia, Nona1 aSmith, Nicholas, L1 aRotter, Jerome, I1 aKors, Jan, A1 aWitteman, Jacqueline, C M1 aHofman, Albert1 aHeckbert, Susan, R1 aO'Donnell, Christopher, J1 aUitterlinden, André, G1 aPsaty, Bruce, M1 aLumley, Thomas1 aLarson, Martin, G1 aStricker, Bruno, H Ch uhttps://chs-nhlbi.org/node/1087