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

被引：295

作者：

Pfeufer, Arne ^{[2
,3
]}

Sanna, Serena ^{[4
]}

Arking, Dan E. ^{[1
]}

Mueller, Martina ^{[5
,6
,7
]}

Gateva, Vesela ^{[8
]}

Fuchsberger, Christian ^{[9
]}

Ehret, Georg B. ^{[1
]}

Orru, Marco ^{[4
]}

Pattaro, Cristian ^{[9
]}

Koettgen, Anna ^{[10
]}

Perz, Siegfried ^{[11
]}

Usala, Gianluca ^{[4
]}

Barbalic, Maja ^{[12
]}

Li, Man ^{[10
]}

Puetz, Benno ^{[13
]}

Scuteri, Angelo ^{[14
]}

Prineas, Ronald J. ^{[15
]}

Sinner, Moritz F. ^{[7
]}

Gieger, Christian ^{[5
]}

Najjar, Samer S. ^{[16
]}

Kao, W. H. Linda ^{[10
]}

Muehleisen, Thomas W. ^{[17
,18
]}

Dei, Mariano

Happle, Christine ^{[2
,3
]}

Moehlenkamp, Stefan ^{[19
]}

Crisponi, Laura ^{[4
]}

Erbel, Raimund ^{[19
]}

Joeckel, Karl-Heinz ^{[20
]}

Naitza, Silvia ^{[4
]}

Steinbeck, Gerhard

Marroni, Fabio ^{[9
]}

Hicks, Andrew A. ^{[9
]}

Lakatta, Edward ^{[16
]}

Mueller-Myhsok, Bertram ^{[13
]}

Pramstaller, Peter P. ^{[9
,21
,22
]}

Wichmann, H-Erich ^{[5
,6
]}

Schlessinger, David ^{[23
]}

Boerwinkle, Eric ^{[12
]}

Meitinger, Thomas ^{[2
,3
]}

Uda, Manuela ^{[4
]}

Coresh, Josef ^{[10
,24
]}

Kaeaeb, Stefan ^{[7
]}

Abecasis, Goncalo R. ^{[8
]}

Chakravarti, Aravinda ^{[1
,24
]}

机构：

[1] Johns Hopkins Univ, McKusick Nathans Inst Genet Med, Baltimore, MD 21218 USA

[2] Helmholtz Ctr Munich, Inst Human Genet, Munich, Germany

[3] Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-80804 Munich, Germany

[4] CNR, Ist Neurogenet & Neurofarmacol, Cagliari, Italy

[5] Helmholtz Ctr Munich, Inst Epidemiol, Munich, Germany

[6] Univ Munich, Inst Informat Biometry & Epidemiol, Munich, Germany

[7] Univ Munich, Klinikum Grosshadern, Dept Med 1, D-80804 Munich, Germany

[8] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA

[9] EURAC European Acad, Inst Med Genet, Bolzano, Italy

[10] Johns Hopkins Univ, Dept Epidemiol, Baltimore, MD USA

[11] Helmholtz Ctr Munich, Inst Med Informat, Munich, Germany

[12] Univ Texas Hlth Sci Ctr, Genet Ctr, Houston, TX USA

[13] Max Planck Inst Psychiat, D-80804 Munich, Germany

[14] Ist Ricovero & Cura Anziani, Unita Operat Geriatria, Rome, Italy

[15] Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA

[16] NIA, Cardiovasc Sci Lab, Gerontol Res Ctr, Baltimore, MD 21224 USA

[17] Univ Bonn, Life & Brain Ctr, Dept Genom, D-5300 Bonn, Germany

[18] Univ Bonn, Inst Human Genet, D-5300 Bonn, Germany

[19] Univ Duisburg Essen, Univ Hosp Essen, W German Heart Ctr, Clin Cardiol, Duisburg, Germany

[20] Univ Duisburg Essen, Univ Hosp Essen, Inst Med Informat Biometry & Epidemiol, Duisburg, Germany

[21] Gen Cent Hosp, Dept Neurol, Bolzano, Italy

[22] Med Univ Lubeck, Dept Neurol, D-23538 Lubeck, Germany

[23] NIA, Genet Lab, Baltimore, MD 21224 USA

[24] Johns Hopkins Univ, Dept Med, Baltimore, MD USA

来源：

NATURE GENETICS | 2009年 / 41卷 / 04期

基金：

美国国家卫生研究院;

关键词：

NOS1 REGULATOR NOS1AP; CARDIAC REPOLARIZATION; GENETIC VARIANT; HEART-FAILURE; POPULATION; DISEASE; MUTATION; KCNH2; RISK; ASSOCIATION;

D O I：

10.1038/ng.362

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：407 / 414

页数：8

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