Identification of genomic loci associated with resting heart rate and shared genetic predictors with all-cause mortality
Identification of genomic loci associated with resting heart rate and shared genetic predictors with all-cause mortality
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DOI：
10.1038/ng.3708
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发表时间：
2016-12-01
期刊：
影响因子：
30.8
通讯作者：
van der Harst, Pim
中科院分区：
文献类型：
--
作者：
Eppinga, Ruben N.;Hagemeijer, Yanick;van der Harst, Pim
静息心率是与寿命相关的可遗传性状。关于遗传对静息心率的影响及其与死亡率的关系，人们知之甚少。我们进行了全基因组关联发现和复制分析，从1990万个遗传变异开始，研究了多达265,046个个体，以确定64个与静息心率相关的基因座（P < 5 x 10（-8））;其中46个是新的。然后，我们使用识别出的遗传变异来研究静息心率与全因死亡率之间的关联。我们观察到，基因预测的静息心率每分钟增加5次与死亡风险增加20%相关（风险比1.20，95%置信区间1.11-1.28，P = 8.20 x 10（-7）），这意味着男性预期寿命减少2.9年，女性减少2.6年。我们的研究结果为静息心率和全因死亡率的共同遗传预测因子提供了证据。
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.