Rationale Large retrospective case-control studies have reported an association between chronic obstructive pulmonary disease (COPD), reduced lung function and an increased risk of Alzheimer’s disease. However, it remains unclear if these diseases are causally linked, or due to shared risk factors. Conventional observational epidemiology suffers from unmeasured confounding and reverse causation. Additional analyses addressing causality are required. Objectives To examine a causal relationship between COPD, lung function and Alzheimer’s disease. Methods Using two-sample Mendelian randomisation, we used single nucleotide polymorphisms (SNPs) identified in a genome wide association study (GWAS) for lung function as instrumental variables (exposure). Additionally, we used SNPs discovered in a GWAS for COPD in those with moderate to very severe obstruction. The effect of these SNPs on Alzheimer’s disease (outcome) was taken from a GWAS based on a sample of 24 807 patients and 55 058 controls. Results We found minimal evidence for an effect of either lung function (OR: 1.02 per SD; 95% CI 0.91 to 1.13; p value 0.68) or liability for COPD on Alzheimer’s disease (OR: 0.97 per SD; 95% CI 0.92 to 1.03; p value 0.40). Conclusion Neither reduced lung function nor liability COPD are likely to be causally associated with an increased risk of Alzheimer’s, any observed association is likely due to unmeasured confounding. Scientific attention and health prevention policy may be better focused on overlapping risk factors, rather than attempts to reduce risk of Alzheimer’s disease by targeting impaired lung function or COPD directly. Data sharing not applicable as no datasets generated and/or analysed for this study. Data used was summary data freely available in supplementary tables or from corresponding authors of respective GWAS.

中文翻译：

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检查肺功能、慢性阻塞性肺病和阿尔茨海默病之间可能的因果关系：孟德尔随机化研究

基本原理 大型回顾性病例对照研究报告了慢性阻塞性肺病 (COPD)、肺功能降低和阿尔茨海默病风险增加之间的关联。然而，尚不清楚这些疾病是否存在因果关系，或者是由于共同的风险因素。传统的观察流行病学存在无法衡量的混杂和反向因果关系。需要对因果关系进行额外的分析。目的 研究 COPD、肺功能和阿尔茨海默病之间的因果关系。方法 使用两样本孟德尔随机化，我们使用在全基因组关联研究 (GWAS) 中确定的肺功能单核苷酸多态性 (SNP) 作为工具变量（暴露）。此外，我们使用了在 GWAS 中发现的 SNP，用于治疗中度至重度阻塞的 COPD。这些 SNP 对阿尔茨海默病（结果）的影响取自基于 24 807 名患者和 55 058 名对照样本的 GWAS。结果 我们发现肺功能（OR：1.02/SD；95% CI 0.91 至 1.13；p 值 0.68）或 COPD 对阿尔茨海默病的影响（OR：0.97/SD；95% CI 0.92 至 1.03）的证据很少; p 值 0.40)。结论 肺功能降低和慢性阻塞性肺病责任都不太可能与阿尔茨海默病风险增加有因果关系，任何观察到的关联都可能是由于无法测量的混杂因素。科学关注和健康预防政策可能会更好地关注重叠的风险因素，而不是试图通过直接针对受损的肺功能或 COPD 来降低阿尔茨海默病的风险。数据共享不适用，因为没有为本研究生成和/或分析的数据集。使用的数据是补充表格中免费提供的摘要数据或来自相应 GWAS 的相应作者的摘要数据。