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

Summary: 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 Mušller5­7, Vesela Gateva8,
Christian Fuchsberger9, Georg B Ehret4, Marco OrruŽ3, Cristian Pattaro9, Anna Košttgen10, Siegfried Perz11,
Gianluca Usala3, Maja Barbalic12, Man Li10, Benno Puštz13, Angelo Scuteri14, Ronald J Prineas15,
Moritz F Sinner7, Christian Gieger5, Samer S Najjar16, W H Linda Kao10, Thomas W Mušhleisen17,18,
Mariano Dei3, Christine Happle1,2, Stefan Mošhlenkamp19, Laura Crisponi3, Raimund Erbel19,
Karl-Heinz Jošckel20, Silvia Naitza3, Gerhard Steinbeck7, Fabio Marroni9, Andrew A Hicks9, Edward Lakatta16,
Bertram Mušller-Myhsok13, Peter P Pramstaller9,21,22, H-Erich Wichmann5,6, David Schlessinger23,
Eric Boerwinkle12, Thomas Meitinger1,2, Manuela Uda3, Josef Coresh10,24, Stefan Kašašb7, Goncžalo R Abecasis8
& Aravinda Chakravarti4,24
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 o 5 Â 10À8. 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.
The lack of serologic biomarkers to predict ventricular tachycardia,


Source: Abecasis, Goncalo - Department of Biostatistics, University of Michigan


Collections: Biology and Medicine; Mathematics