Variants near CHRNA3/5 and APOE have age- and sex-related effects on human lifespan
Variants near CHRNA3/5 and APOE have age- and sex-related effects on human lifespan
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DOI：
10.1038/ncomms11174
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发表时间：
2016-03-01
影响因子：
16.6
通讯作者：
Wilson, James F.
中科院分区：
文献类型：
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作者：
Joshi, Peter K.;Fischer, Krista;Wilson, James F.
寿命是一个巨大的个人利益的特征。然而，对人类寿命的生物学基础的研究受到死亡时间过长的阻碍。在一个新的大型数据集（英国生物银行）中，使用一种新的方法回归（272，081）父母寿命超过40岁的参与者基因型，我们在这里显示，载脂蛋白E和烟碱乙酰胆碱受体亚基α 5基因附近的常见变异与寿命相关。这种影响具有很强的性别和年龄依赖性，APOE β 4对母体寿命的影响不同（P = 4.2 × 10（-15），影响-1.24年的母亲生活每插补风险等位基因的父母;性别差异，P = 0.011），CHRNA 3/5附近的基因座差异影响父亲的寿命（P = 4.8 x 10（-11），每个等位基因的效应为-0.86岁;性别差异P = 0.075）。在这两个基因座上的风险等位基因的罕见纯合子携带者预计寿命短3.3-3.7年。
Lifespan is a trait of enormous personal interest. Research into the biological basis of human lifespan, however, is hampered by the long time to death. Using a novel approach of regressing (272,081) parental lifespans beyond age 40 years on participant genotype in a new large data set (UK Biobank), we here show that common variants near the apolipoprotein E and nicotinic acetylcholine receptor subunit alpha 5 genes are associated with lifespan. The effects are strongly sex and age dependent, with APOE epsilon 4 differentially influencing maternal lifespan (P = 4.2 x 10(-15), effect -1.24 years of maternal life per imputed risk allele in parent; sex difference, P = 0.011), and a locus near CHRNA3/5 differentially affecting paternal lifespan (P = 4.8 x 10(-11), effect -0.86 years per allele; sex difference P = 0.075). Rare homozygous carriers of the risk alleles at both loci are predicted to have 3.3-3.7 years shorter lives.