评估基于人口的西班牙裔队列中阿尔茨海默病的多基因风险评分预测表现,使用单种和多种祖先模型
Yuexuan Xu1,2, Min Qiao1,2, Tamil I Gunasekaran1,2
1Taub Institute for Research on Alzheimer's Disease and the Aging Brain, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY, USA.
Lancet regional health. Americas
|August 1, 2025
概括
新的多祖先多基因风险评分 (PRS) 改善了西班牙裔的阿尔茨海默氏病 (AD) 风险预测. 这些先进的PRS模型,利用各种遗传数据,在预测AD方面显示出与APOE基因相比或更高的性能.
科学领域:
- 遗传学 是一个遗传学.
- 神经科学是一个神经科学.
- 公共卫生 公共卫生
背景情况:
- 多基因风险评分 (PRS) 是欧洲人口中阿尔茨海默病 (AD) 风险的确立预测因素.
- 在西班牙裔人口中,PRS的实用性仍未得到充分研究,这凸显了需要包括祖先在内的遗传风险预测的需要.
- 多祖先基因组广泛关联研究 (GWAS) 提供了一条在不同群体中提高PRS准确性的途径.
研究的目的:
- 评估单祖先和多祖先PRS模型在预测西班牙裔中AD风险方面的表现.
- 将新的多祖先PRS方法与传统的以GWAS为中心的方法进行比较.
- 评估PRS对临床AD,事件AD,认知和血生物标志物的预测能力.
主要方法:
- 利用来自非洲,欧洲和西班牙裔人口的GWAS数据来构建PRS.
- 采用了以GWAS为重点和以新方法为重点的多祖先PRS衍生方法.
- 在2961名西班牙裔个人中评估PRS性能,使用交叉验证和生物标记数据.
主要成果:
- 以方法为重点的多祖先PRS,不包括APOE,优于单个祖先和以GWAS为重点的多祖先PRS.
- 专注于顶部方法的PRS解释了事件AD变异的高达3.9%,与APOE.
- 在预测Aβ和P-tau生物标志物方面,PRS显示出差异性表现,这表明了不同的生物学见解.
结论:
- 将新的多祖先PRS方法与多种GWAS数据相结合,显著提高了西班牙裔人口中AD风险预测.
- 多祖先PRS为个性化的AD风险评估提供了一个强大的工具,补充了APOE等现有的遗传标记.
- 这些发现强调了包容性遗传研究对于公平的疾病风险预测的重要性.
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