Common variants at ten loci modulate the QT interval duration in the QTSCD Study

Arne Pfeufer, Serena Sanna, Dan E. Arking, Martina Müller, Vesela Gateva, Christian Fuchsberger, Georg B. Ehret, Marco Orr, Cristian Pattaro, Anna Köttgen, Siegfried Perz, Gianluca Usala, Maja Barbalic, Man Li, Benno Pütz, Angelo Scuteri, Ronald J. Prineas, Moritz F. Sinner, Christian Gieger, Samer S. NajjarW. H Linda Kao, Thomas W. Mühleisen, Mariano Dei, Christine Happle, Stefan Möhlenkamp, Laura Crisponi, Raimund Erbel, Karl Heinz Jöckel, Silvia Naitza, Gerhard Steinbeck, Fabio Marroni, Andrew A. Hicks, Edward Lakatta, Bertram Müller-Myhsok, Peter P. Pramstaller, H. Erich Wichmann, David Schlessinger, Eric Boerwinkle, Thomas Meitinger, Manuela Uda, Josef Coresh, Stefan Kääb, Gonçalo R. Abecasis, Aravinda Chakravarti

Research output: Contribution to journalArticle

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 × 108. 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.

Original languageEnglish
Pages (from-to)407-414
Number of pages8
JournalNature Genetics
Volume41
Issue number4
DOIs
Publication statusPublished - Apr 2009

    Fingerprint

ASJC Scopus subject areas

  • Genetics

Cite this

Pfeufer, A., Sanna, S., Arking, D. E., Müller, M., Gateva, V., Fuchsberger, C., Ehret, G. B., Orr, M., Pattaro, C., Köttgen, A., Perz, S., Usala, G., Barbalic, M., Li, M., Pütz, B., Scuteri, A., Prineas, R. J., Sinner, M. F., Gieger, C., ... Chakravarti, A. (2009). Common variants at ten loci modulate the QT interval duration in the QTSCD Study. Nature Genetics, 41(4), 407-414. https://doi.org/10.1038/ng.362