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基因组信息化痴呆风险报告改善了跨不同人群的阿尔茨海默病风险预测. 量身定制的遗传和临床风险评分增强了个性化预防策略,以获得公平的痴呆症护理.

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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.
  • 流行病学 流行病学

背景情况:

  • 基因组知情痴呆风险报告 (GIDRR) 可以改善阿尔茨海默病 (AD) 风险预测和预防.
  • 目前的AD风险模型往往缺乏在不同人群中的验证,主要来自非拉丁裔白人 (NLW) 个人.
  • 这项研究评估了不同群体的AD临床和多基因风险评分 (CRS和PRS),检查了它们与家族病史 (FHx) 和APOE对痴呆风险的综合影响.

研究的目的:

  • 评估AD临床风险评分 (CRS) 和多基因风险评分 (PRS) 在不同人群中的预测准确度.
  • 检查CRS,PRS,家族病史 (FHx) 和APOE对事件痴呆症的综合影响.
  • 为个性化预防策略开发和验证基因组知情痴呆风险报告 (GIDRR).

主要方法:

  • 构建了三种AD-PRS模型 (单祖先,多祖先,交叉祖先),不包括ADSP队列中的APOE (N=18,623),具有多种遗传祖先组.
  • 评估了AD-PRS与AD的关联,使用后勤回归,调整共变量.
  • 在NACC和ADNI队列 (N=20,755) 中开发和评估了两种CRS (CAIDE和mCAIDE),包括各种报告的种群,评估与MCI/AD的关联.
  • 构建了一个集成mCAIDE,FHx,APOE*ε4和高AD-PRS-CSx的GIDRR,并使用Cox比例危险模型来估计痴呆症进展风险.

主要成果:

  • AD-PRS模型在1KG-EUR类,1KG-AFR类和1KG-AMR类人群中显示出预测价值,特别是多祖先和交叉祖先的PRS.
  • CAIDE得分预测了亚洲,拉丁和NLW参与者的MCI/AD,而mCAIDE得分显示了所有群体的显著关联,在亚洲人中最强.
  • GIDRR证明了AD风险的剂量依赖性增加:一个指标 (27%的增加),两个 (83%),三个 (两倍的风险) 和四个 (五倍的增加).

结论:

  • 结合遗传祖先和种族/种族的AD PRS和CRS模型显示了更好的可转移性和预测准确性.
  • 基因组信息化风险报告可以促进公平和个性化的痴呆症预防.
  • 这些发现支持开发针对阿尔茨海默病的包容性风险预测工具.