Pfeufer Arne, Sanna Serena, Arking Dan E, Müller Martina, Gateva Vesela, Fuchsberger Christian, Ehret Georg B, Orrú Marco, Pattaro Cristian, Köttgen Anna, Perz Siegfried, Usala Gianluca, Barbalic Maja, Li Man, Pütz Benno, Scuteri Angelo, Prineas Ronald J, Sinner Moritz F, Gieger Christian, Najjar Samer S, Kao W H Linda, Mühleisen Thomas W, Dei Mariano, Happle Christine, Möhlenkamp Stefan, Crisponi Laura, Erbel Raimund, Jöckel Karl-Heinz, Naitza Silvia, Steinbeck Gerhard, Marroni Fabio, Hicks Andrew A, Lakatta Edward, Müller-Myhsok Bertram, Pramstaller Peter P, Wichmann H-Erich, Schlessinger David, Boerwinkle Eric, Meitinger Thomas, Uda Manuela, Coresh Josef, Kääb Stefan, Abecasis Gonçalo R, Chakravarti Aravinda
Institute of Human Genetics, Helmholtz Center Munich, Germany.
Nat Genet. 2009 Apr;41(4):407-14. doi: 10.1038/ng.362. Epub 2009 Mar 22.
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 x 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.
QT间期是衡量心脏复极化的指标，延长或缩短时会增加室性心律失常和心源性猝死（SCD）的风险。已知NOS1AP中的一个常见变异会影响复极化。我们分析了来自五个基于人群的队列（ARIC、KORA、撒丁岛研究、GenNOVA和HNR）的全基因组数据，这些队列共有15842名欧洲血统个体，以确认NOS1AP的关联并在P < 5 x 10(-8)水平上鉴定出另外九个基因座。四个基因座位于单基因长QT综合征基因KCNQ1、KCNH2、SCN5A和KCNJ2附近。另外两个基因座包括ATP1B1和PLN，这两个基因具有已确定的电生理功能，而另外三个分别映射到RNF207、LITAF附近以及NDRG4 - GINS3 - SETD6 - CNOT1内，所有这些基因此前均未被认为与心脏电生理有关。这些结果与QTGEN联盟的一篇随附论文一起，确定了室性心律失常和心源性猝死的新候选基因。
