Common variants at ten loci influence QT interval duration in the QTGEN Study

C Newton-Cheh, Mark Eijgelsheim, KM Rice, PIW de Bakker, XY Yin, Karol Estrada Gil, JC Bis, K Marciante, Fernando Rivadeneira, PA Noseworthy, N Sotoodehnia, NL Smith, JI Rotter, Jan Kors, JCM Witteman, Bert Hofman, SR Heckbert, CJ O'Donnell, André Uitterlinden, BM PsatyT Lumley, MG Larson, Bruno Stricker

Research output: Contribution to journalArticleAcademicpeer-review

342 Citations (Scopus)


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.
Original languageUndefined/Unknown
Pages (from-to)399-406
Number of pages8
JournalNature Genetics
Issue number4
Publication statusPublished - 2009

Cite this