PT - JOURNAL ARTICLE AU - Daniel Higbee AU - Raquel Granell AU - Esther Walton AU - Roxanna Korologou-Linden AU - George Davey Smith AU - James Dodd TI - Examining the possible causal relationship between lung function, COPD and Alzheimer’s disease: a Mendelian randomisation study AID - 10.1136/bmjresp-2020-000759 DP - 2021 Jul 01 TA - BMJ Open Respiratory Research PG - e000759 VI - 8 IP - 1 4099 - http://bmjopenrespres.bmj.com/content/8/1/e000759.short 4100 - http://bmjopenrespres.bmj.com/content/8/1/e000759.full SO - BMJ Open Resp Res2021 Jul 01; 8 AB - 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.