Common variants at ten loci influence QT interval duration in the QTGEN Study

被引：321

作者：

Newton-Cheh, Christopher ^{[1
,2
,3
,4
]}

Eijgelsheim, Mark ^{[5
]}

Rice, Kenneth M. ^{[6
]}

de Bakker, Paul I. W. ^{[2
,3
,7
]}

Yin, Xiaoyan ^{[4
,8
]}

Estrada, Karol ^{[9
]}

Bis, Joshua C. ^{[10
]}

Marciante, Kristin ^{[10
]}

Rivadeneira, Fernando ^{[5
,9
]}

Noseworthy, Peter A. ^{[1
]}

Sotoodehnia, Nona ^{[10
,11
]}

Smith, Nicholas L. ^{[10
,12
,13
]}

Rotter, Jerome I. ^{[14
]}

Kors, Jan A. ^{[15
]}

Witteman, Jacqueline C. M. ^{[5
,16
]}

Hofman, Albert ^{[5
,16
]}

Heckbert, Susan R. ^{[10
,12
,17
]}

O'Donnell, Christopher J. ^{[4
,18
,19
]}

Uitterlinden, Andre G. ^{[5
,9
,16
]}

Psaty, Bruce M. ^{[10
,12
,17
,20
]}

Lumley, Thomas ^{[6
]}

Larson, Martin G. ^{[4
,8
]}

Stricker, Bruno H. Ch ^{[5
,9
,15
,16
,21
]}

机构：

[1] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Ctr Human Genet Res, Boston, MA 02114 USA

[2] Harvard Univ, Broad Inst, Program Med & Populat Genet, Cambridge, MA 02138 USA

[3] MIT, Cambridge, MA 02139 USA

[4] NHLBI, Framingham Heart Study, Framingham, MA USA

[5] Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands

[6] Univ Washington, Dept Biostat, Seattle, WA 98195 USA

[7] Brigham & Womens Hosp, Dept Med, Div Genet, Boston, MA 02115 USA

[8] Boston Univ, Dept Math & Stat, Boston, MA 02215 USA

[9] Erasmus MC, Dept Internal Med, Rotterdam, Netherlands

[10] Univ Washington, Cardiovasc Hlth Res Unit, Seattle, WA 98195 USA

[11] Univ Washington, Dept Med, Sch Med, Div Cardiol, Seattle, WA 98195 USA

[12] Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA

[13] Vet Adm Off Res & Dev, Seattle Epidemiol Res Ctr, Seattle, WA USA

[14] Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA

[15] Erasmus MC, Dept Med Informat, Rotterdam, Netherlands

[16] Netherlands Genom Initiat Sponsored Netherlands C, NL-3000 CA Rotterdam, Netherlands

[17] Grp Hlth, Ctr Hlth Studies, Seattle, WA USA

[18] NHLBI, Bethesda, MD 20892 USA

[19] Massachusetts Gen Hosp, Div Cardiol, Boston, MA 02114 USA

[20] Univ Washington, Dept Hlth Serv, Seattle, WA 98195 USA

[21] Inspectorate Hlth Care, The Hague, Netherlands

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; SUDDEN CARDIAC DEATH; PHOSPHOLAMBAN GENE; HEART; ASSOCIATION; SCN5A; KCNH2; REPOLARIZATION; POLYMORPHISM; MUTATION;

D O I：

10.1038/ng.364

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

QT interval duration, reflecting myocardial repolarization on the electrocardiogram, is a heritable risk factor for sudden cardiac death and drug-induced arrhythmias. We conducted a meta-analysis of three genome-wide association studies in 13,685 individuals of European ancestry from the Framingham Heart Study, the Rotterdam Study and the Cardiovascular Health Study, as part of the QTGEN consortium. We observed associations at P < 5 x 10(-8) with variants in NOS1AP, KCNQ1, KCNE1, KCNH2 and SCN5A, known to be involved in myocardial repolarization and mendelian long-QT syndromes. Associations were found at five newly identified loci, including 16q21 near NDRG4 and GINS3, 6q22 near PLN, 1p36 near RNF207, 16p13 near LITAF and 17q12 near LIG3 and RFFL. Collectively, the 14 independent variants at these 10 loci explain 5.4-6.5% of the variation in QT interval. These results, together with an accompanying paper, offer insights into myocardial repolarization and suggest candidate genes that could predispose to sudden cardiac death and drug-induced arrhythmias.

引用

页码：399 / 406

页数：8

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