甲基化时钟无法预测遗传混合个体的年龄或阿尔茨海默病风险
Sebastián Cruz-González1,2,3, Esther Gu4, Lissette Gomez4
1Biological and Medical Informatics Program, University of California, San Francisco, San Francisco, CA.
bioRxiv : the preprint server for biology
|October 28, 2024
概括
在基因多样化的群体中,DNA甲基化钟在预测年龄和阿尔茨海默病风险方面显示出较低的准确性,特别是那些具有非洲血统的人群中. 这凸显了需要在不同祖先之间改进时钟的便携性.
科学领域:
- 基因组学就是基因组学.
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 神经退行性疾病 神经退行性疾病
背景情况:
- 由DNA甲基化衍生的表观遗传时钟是衰老和与年龄相关的疾病 (如阿尔茨海默病) 的潜在生物标志物.
- 这些时钟在基因多样化的队列中缺乏验证.
研究的目的:
- 评估DNA甲基化时钟在预测年龄和识别遗传多样性人群中的年龄加速方面的准确性和性能.
- 评估遗传祖先对甲基化时钟性能的影响.
主要方法:
- 分析了来自621名非洲裔美国人,西班牙裔和白人队伍的DNA甲基化数据,包括阿尔茨海默病患者和对照组.
- 评估已建立的甲基化时钟,以预测年龄的准确性和识别年龄加速.
主要成果:
- 与白人队列相比,甲基化钟在预测遗传混合个体的时间年龄方面表现出较低的准确性,特别是那些具有非洲血统的个体.
- 时钟在混合的AD病例和对照中没有一致检测到年龄加速.
- 影响时钟CpG的甲基化定量特征位 (meQTLs) 在非洲遗传祖先中发现频率更高.
结论:
- 目前的DNA甲基化时钟在不同的遗传祖先中表现出有限的可移植性和准确性.
- 遗传血统,特别是非洲血统,显著影响甲基化时钟的性能.
- 需要进行进一步的研究,以开发更强大,更普遍适用的表观遗传钟,用于年龄和疾病风险预测.
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