综合神经退行和血管风险的多基因评分为痴呆症风险分层提供信息
Tim D'Aoust1, Santiago Clocchiatti-Tuozzo2,3, Cyprien A Rivier2,3
1Bordeaux Population Health Center, INSERM, UMR U1219, University of Bordeaux, Bordeaux, France.
概括
综合性多基因风险评分 (iPRS-DEM) 识别了超出APOE的痴呆风险,改善了跨不同人群的预测. 该工具增强了临床试验和预防计划的风险分层.
科学领域:
- 遗传学 是一个遗传学.
- 神经科学是一个神经科学.
- 流行病学 流行病学
背景情况:
- 综合性多基因风险评分 (iPRS) 可以捕捉导致痴呆的神经退行和血管因素.
- 识别患有痴呆症高风险的个体对于有效的干预和改进的预测模型至关重要.
研究的目的:
- 在欧洲和东亚人口中开发和评估痴呆症综合性多基因风险评分 (iPRS-DEM).
- 评估iPRS-DEM在痴呆风险分层中的表现,独立地和与APOE ε4结合.
- 确定iPRS-DEM在不同队列的概括性,包括社区居住的老年人和记忆诊所的参与者.
主要方法:
- 使用阿尔茨海默病的遗传数据和欧洲人的23种血管/神经退行性特征 (不包括APOE) 开发了iPRS-DEM.
- 在多个队列中评估了iPRS-DEM:社区居住的老年人 (N=3702),多祖先生物库 (N=130,797名欧洲人;105,404名非欧洲人) 和记忆诊所参与者 (N=2032).
主要成果:
- 在欧洲,东亚和记忆诊所队列中,iPRS-DEM与APOE独立于痴呆风险有关.
- 通过iPRS-DEM预测的风险与社区居民的临床因素相当,并且在记忆诊所患者中表现改善.
- 将iPRS-DEM与APOE ε4结合,确定了四个遗传风险组,在APOE ε4+/iPRS-DEM+记忆诊所参与者中观察到的风险增加了五倍.
结论:
- iPRS-DEM有效地捕捉了神经退行和血管对痴呆的贡献,提供了超出APOE和AD-PRS的额外遗传风险信息.
- 在完善痴呆风险分层方面,iPRS-DEM显得有前途,特别是在与APOE ε4相结合时,用于临床试验丰富和预防计划.
- 结果表明iPRS-DEM在不同人群和临床环境中具有普遍性和可传输性.
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