Article abstract
Nature Genetics 41, 407 - 414 (2009)
Published online: 22 March 2009 | doi:10.1038/ng.362
Common variants at ten loci modulate the QT interval duration in the QTSCD Study
Arne Pfeufer1,2,25, Serena Sanna3,25, Dan E Arking4,25, Martina Müller5,6,7, Vesela Gateva8, Christian Fuchsberger9, Georg B Ehret4, Marco Orrú3, Cristian Pattaro9, Anna Köttgen10, Siegfried Perz11, Gianluca Usala3, Maja Barbalic12, Man Li10, Benno Pütz13, Angelo Scuteri14, Ronald J Prineas15, Moritz F Sinner7, Christian Gieger5, Samer S Najjar16, W H Linda Kao10, Thomas W. Mühleisen17,18, Mariano Dei3, Christine Happle1,2, Stefan Möhlenkamp19, Laura Crisponi3, Raimund Erbel19, Karl-Heinz Jöckel20, Silvia Naitza3, Gerhard Steinbeck7, Fabio Marroni9, Andrew A Hicks9, Edward Lakatta16, Bertram Müller-Myhsok13, Peter P Pramstaller9,21,22, H-Erich Wichmann5,6, David Schlessinger23, Eric Boerwinkle12, Thomas Meitinger1,2, Manuela Uda3, Josef Coresh10,24, Stefan Kääb7, Gonçalo R Abecasis8 & Aravinda Chakravarti4,24
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 
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.
- Institute of Human Genetics, Helmholtz Center Munich, Germany.
- Institute of Human Genetics, Klinikum rechts der Isar der Technischen Universität München, Munich, Germany.
- Istituto di Neurogenetica e Neurofarmacologia, CNR, Monserrato, Cagliari, Italy.
- McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
- Institute of Epidemiology, Helmholtz Center Munich, Germany.
- Institute of Informatics, Biometry and Epidemiology, Ludwig-Maximilians-Universität, Munich, Germany.
- Department of Medicine I, Klinikum Grosshadern, Munich, Germany.
- Center for Statistical Genetics, Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA.
- Institute of Genetic Medicine, EURAC European Academy, Bolzano, Italy.
- Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland, USA.
- Institute of Medical Informatics, Helmholtz Center Munich, Germany.
- Genetics Center, University of Texas Health Science Center, Houston, Texas, USA.
- Statistical Genetics, Max Planck Institute of Psychiatry, Munich, Germany.
- Unità Operativa Geriatria, Istituto Ricovero e Cura per Anziani, Rome, Italy.
- Wake Forest University School of Medicine, Winston-Salem, North Carolina, USA.
- Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, Baltimore, Maryland, USA.
- Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
- Institute of Human Genetics, University of Bonn, Bonn, Germany.
- Clinic of Cardiology, West German Heart Center, University Hospital of Essen, University Duisburg-Essen, Germany.
- Institute for Medical Informatics, Biometry and Epidemiology, University Hospital of Essen, University Duisburg-Essen, Germany.
- Department of Neurology, General Central Hospital, Via Bohler 5, Bolzano, Italy.
- Department of Neurology, University of Lübeck, Lübeck, Germany.
- Laboratory of Genetics, National Institute on Aging, Baltimore, Maryland, USA.
- Department of Medicine, Johns Hopkins University, Baltimore, Maryland, USA.
- These authors contributed equally to this work.
Correspondence to: Aravinda Chakravarti4,24 e-mail: aravinda@jhmi.edu
Correspondence to: Gonçalo R Abecasis8 e-mail: goncalo@umich.edu
Correspondence to: Arne Pfeufer1,2,25 e-mail: arne.pfeufer@helmholtz-muenchen.de
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