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心血管疾病 (CVD) 显著增加阿尔茨海默氏症和相关痴呆症 (ADRD) 的风险,特别是APOE-ε4.4. 基因与环境的相互作用显示了附加效应,突出了对痴呆风险的综合遗传和并发症评估的需要.

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科学领域:

  • 神经科学是一个神经科学.
  • 遗传学 遗传学 是一个
  • 流行病学 流行病学

背景情况:

  • 心血管疾病 (CVD),如外周动脉疾病 (PAD) 和冠状动脉疾病 (CAD) 是阿尔茨海默病和相关痴呆症 (ADRD) 的确立危险因素.
  • APOE-ε4变体是AD的主要遗传风险因素,与胆固醇和甘油三水平的增加有关,进一步增加心血管疾病的风险.
  • 本研究调查了APOE-ε4和心血管疾病对美国退伍军人事务部百万退伍军人计划 (MVP) 中ADRD患病率的综合影响.

研究的目的:

  • 检查APOE-ε4基因型与心血管疾病 (CVD) 对阿尔茨海默氏症和相关痴呆症 (ADRD) 患病率的相互作用影响.
  • 评估与ADRD相关的APOE-ε4和一系列心血管疾病 (PAD,CAD,心肌梗塞,高血压,高脂血症) 之间的基因环境 (GxE) 相互作用.
  • 通过添加尺度指标 (相对因相互作用而导致的过度风险 - - RERI) 提供更易于解释的相互作用指标.

主要方法:

  • 利用了65岁以上的大量欧洲祖先的MVP参与者队列 (n=11,112个ADRD病例,170,361个对照) 和基因型数据.
  • 使用GEM软件包进行横截面物流回归分析,以测试GxE相互作用.
  • 使用经过验证的算法来识别ADRD,心肌梗塞 (MI),PAD,CAD,高血压和高脂血症,使用ICD代码和Phecodes.

主要成果:

  • 心血管疾病与ADRD显著的主要影响关联 (ORs 1.55-1.82,p < 10^99).
  • 综合和单个CVD相互作用术语都显示了APOE-ε4和CVD之间的显著GxE相互作用 (p值低至7x10^-8).
  • RERI估计证实了显著的积极的添加剂规模相互作用,表明APOE-ε4和心血管疾病对ADRD的综合风险大于它们的单个风险的总和.

结论:

  • APOE-ε4和心血管疾病之间的添加量级相互作用提供了对它们对ADRD患病率的联合影响的更直接的解释.
  • 在患有心血管疾病的个体中,ADRD患病率随着遗传APOE-ε4等位基因的数量增加而增加.
  • 将遗传信息 (APOE-ε4) 与健康并发症数据 (CVD) 整合起来,可以提高痴呆风险评估的准确性,特别是在老兵群体中.