Identification of genomic loci associated with resting heart rate and shared genetic predictors with all-cause mortality

被引：118

作者：

Eppinga, Ruben N. ^{[1
]}

Hagemeijer, Yanick ^{[1
]}

Burgess, Stephen ^{[2
]}

Hinds, David A. ^{[3
]}

Stefansson, Kari ^{[4
,5
]}

Gudbjartsson, Daniel F. ^{[4
,6
]}

van Veldhuisen, Dirk J. ^{[1
]}

Munroe, Patricia B. ^{[7
,8
]}

Verweij, Niek ^{[1
]}

van der Harst, Pim ^{[1
,9
,10
]}

机构：

[1] Univ Groningen, Univ Med Ctr Groningen, Dept Cardiol, Groningen, Netherlands

[2] Univ Cambridge, Dept Publ Hlth & Primary Care, Cambridge, England

[3] 23andMe Inc, Mountain View, CA USA

[4] Amgen Inc, deCODE Genet, Reykjavik, Iceland

[5] Univ Iceland, Fac Med, Reykjavik, Iceland

[6] Univ Iceland, Sch Engn & Nat Sci, Reykjavik, Iceland

[7] Queen Mary Univ London, William Harvey Res Inst, Barts & London Sch Med & Dent, Dept Clin Pharmacol, London, England

[8] Queen Mary Univ London, NIHR Barts Cardiovasc Biomed Res Unit, London, England

[9] Univ Groningen, Univ Med Ctr Groningen, Dept Genet, Groningen, Netherlands

[10] Netherlands Heart Inst, Durrer Ctr Cardiogenet Res, Utrecht, Netherlands

来源：

NATURE GENETICS | 2016年 / 48卷 / 12期

基金：

英国惠康基金;

关键词：

CORONARY-ARTERY-DISEASE; PLACEBO-CONTROLLED TRIAL; WIDE ASSOCIATION; RISK-FACTOR; UK BIOBANK; FOLLOW-UP; OUTCOMES; HYPERTENSION; IVABRADINE; FAILURE;

D O I：

10.1038/ng.3708

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Resting heart rate is a heritable trait correlated with life span. Little is known about the genetic contribution to resting heart rate and its relationship with mortality. We performed a genome-wide association discovery and replication analysis starting with 19.9 million genetic variants and studying up to 265,046 individuals to identify 64 loci associated with resting heart rate (P < 5 x 10(-8)); 46 of these were novel. We then used the genetic variants identified to study the association between resting heart rate and all-cause mortality. We observed that a genetically predicted resting heart rate increase of 5 beats per minute was associated with a 20% increase in mortality risk (hazard ratio 1.20, 95% confidence interval 1.11-1.28, P = 8.20 x 10(-7)) translating to a reduction in life expectancy of 2.9 years for males and 2.6 years for females. Our findings provide evidence for shared genetic predictors of resting heart rate and all-cause mortality.

引用

页码：1557 / 1563

页数：7

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