基础科学和病原发生学
Mohsen Sharifi Tabar1, Dongyu Wang2, Gina M Peloso2
1The University of Texas Health Science Center at San Antonio, San Antonio, TX, USA.
Alzheimer's & dementia : the journal of the Alzheimer's Association
|December 25, 2025
概括
遗传因素影响阿尔茨海默病 (AD) 的时间. 这项研究将APOE识别为关键和新型位点,如ROR1,ROR2,ADAMTS8和SHISA6,这表明随着时间的推移对AD发病有着不同的遗传影响.
科学领域:
- 遗传学和基因组学 遗传学和基因组学
- 神经科学是一个神经科学.
- 精准医学是一门精准的医学.
背景情况:
- 阿尔茨海默病 (AD) 风险受到复杂的遗传因素的影响,全基因组关联研究 (GWAS) 确定了几个AD相关的位置.
- 虽然遗传因素在AD发病时间上起作用,但专门关注AD发病时间的GWAS是有限的.
研究的目的:
- 使用全基因组测序 (WGS) 数据识别与阿尔茨海默病 (AD) 发病时间相关的遗传变异.
- 为了研究遗传因素在AD发病时间上的作用,跨越多样化的祖先群体.
主要方法:
- 利用了来自阿尔茨海默氏病测序项目 (ADSP) 和Trans-Omics for Precision Medicine (TOPMed) 计划的数据,其中包括超过14,000名具有时间到AD和WGS数据的个人.
- 在非西班牙裔白人,黑人和西班牙裔人口中,采用了特定于祖先的考克斯比例危险模型,调整了人口统计和遗传因素.
- 分析的变体具有小等位基频率 (MAF) >1%.
主要成果:
- 在ADSP和TOPMed数据集中,APOE地区与AD发病时间的关联最强.
- 对于映射到ROR1,ROR2,ADAMTS8和SHISA6的变异,涉及神经元发育,突触功能和神经可塑性的基因,已达到全基因组显著性.
- 在时间到AD的GWAS结果和传统的病例控制GWAS结果之间观察到有限的重叠,除了APOE.
结论:
- 初步发现证实了APOE在AD发病时间方面的关键作用,并确定了新的潜在位置.
- 与AD总体风险相比,随着时间的推移,不同的遗传因素可能会影响AD风险.
- 进一步的元分析,罕见变体评估和多祖先分析正在进行中,以扩大发现.
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