Introduction: Several Mendelian randomization studies have been conducted, which identified multiple risk factors for Alzheimer's disease (AD). However, they typically focus on a few pre-selected risk factors. Methods: Two-sample Mendelian randomization (MR) study was used to systematically examine the potential causal associations of 1,054 risk factors/medical conditions and 28 drugs with the risk of late-onset AD. To correct for multiple comparisons, the false discovery rate was set at <0.05. Results: There were strong evidence of a causal association between glioma risk, reduced trunk fat-free mass, lower education levels, lower intelligence and a higher risk of AD. For 28 investigated treatments (such as antihypertensive drugs), we found limited evidence for their associations. Conclusion: MR found robust evidence of causal associations between glioma, trunk fat-free and AD. Our study also confirms that higher educational attainment and higher intelligence are associated with a reduced risk of AD.

中文翻译：

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系统地确定可改变的危险因素和阿尔茨海默氏病的药物替代疗法：孟德尔随机分析

简介：已经进行了几项孟德尔随机研究，确定了阿尔茨海默氏病（AD）的多个危险因素。但是，他们通常关注一些预先选择的风险因素。方法：采用两样本孟德尔随机（MR）研究系统地检查了1,054个危险因素/医学状况和28种药物与迟发性AD风险的潜在因果关系。为了校正多个比较，将错误发现率设置为<0.05。结果：有强有力的证据表明神经胶质瘤风险，躯干无脂肪量减少，教育水平较低，智力较低和AD风险较高之间存在因果关系。对于28种被调查的治疗方法（例如降压药），我们发现其关联性的证据有限。结论：MR发现了胶质瘤，躯干无脂肪和AD之间因果联系的有力证据。我们的研究还证实，较高的学历和较高的智力与降低AD风险有关。