人类长寿的遗传关联被丰富为致癌基因
Junyoung Park1, Andrés Peña-Tauber1, Lia Talozzi1
1Department of Neurology and Neurological Sciences, Stanford University, Stanford, CA, 94305, USA.
medRxiv : the preprint server for health sciences
|August 12, 2024
概括
遗传变异影响人类寿命. 这项研究确定了与长寿和寿命缩短相关的基因,特别是与癌症和克隆性血液形成相关的基因,为精确的健康和早期遗传测试提供了洞察力.
科学领域:
- 遗传学和基因组学 遗传学和基因组学
- 长寿研究研究 长寿研究
- 精确的健康 精确的健康
背景情况:
- 人类寿命是一个复杂的特征,受遗传和环境因素的影响.
- 了解对生存和死亡率的遗传贡献对于推进精密健康至关重要.
- 以前的研究已经将特定的遗传变异与寿命联系起来,但正在进行全面分析.
研究的目的:
- 研究常见和罕见的遗传变异与人类寿命的关联.
- 确定与长寿相关的遗传位置和与寿命缩短相关的基因.
- 探索遗传变异在癌症倾向和早期死亡率中的作用.
主要方法:
- 对欧洲血统的英国生物库参与者进行了生存分析 (死亡时的年龄为N=35,551,最后已知的年龄为N=358,282).
- 分析了常见的遗传变体和罕见的非同义变体 (功能丧失和致病误解) 的负担.
- 用一种方向不可知的SKAT-O方法来确定额外的重要关联.
主要成果:
- 发现了三个与长寿相关的位点:APOE,ZSCAN23和MUC5B.
- 六个基因 (TET2,ATM,BRCA2,CKMT1B,BRCA1,ASXL1) 显示了功能丧失变体负担与寿命缩短之间的关联.
- 八个基因 (DNMT3A,SF3B1,CHL1,TET2,PTEN,SOX21,TP53,SRSF2) 显示了致病性误解变异负担与寿命缩短之间的关联.
- SKAT-O确定了与C1orf52,TERT,IDH2和RLIM的关联,将端粒功能和瘤发生与寿命联系起来.
- 已识别的变异主要与癌症途径和克隆性血液形成有关.
结论:
- 遗传因素显著影响人类寿命,特定变异影响寿命和死亡风险.
- 这些发现强调了遗传变异在普遍死亡原因,特别是癌症中的重要性.
- 早期遗传测试可以识别容易患癌症和/或过早死亡的个体,从而实现个性化的健康策略.
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