Mendelian randomization study shows a causal effect of asthma on chronic obstructive pulmonary disease risk

Abstract

Background This study was performed to explore the causal association between asthma and chronic obstructive pulmonary disease(COPD). Methods We obtained summary statistics for asthma from 408,442 Europeans in an open genome-wide association study (GWAS) from the UK Biobank to select strongly associated single nucleotide polymorphisms that could serve as instrumental variables for asthma (P Results In the UVMR analysis, asthma increased the risk of COPD, with an odds ratio (OR) of 1.27 (95% confidence interval (CI) = 1.16–1.39, P = 5.44×10−7). Estimates were consistent in MVMR analyses by the adjustments of smoking initiation, age of smoking initiation, cigarettes per day, PM 2.5, and the combination of the above factors. In the reverse MR analysis, there was no evidence of a causal effect of COPD on asthma risk(OR = 1.02, 95% CI = 0.97–1.07, P = 0.3643). In the replication MR analysis, asthma still increased the risk of COPD. Sensitivity analyses validated the robustness of the above associations. Conclusions We found that genetically predicted asthma was positively associated with the risk of COPD. Additionally, there was no evidence that COPD increases the risk of asthma. Further clarification of this link and underlying mechanisms is needed to identify feasible measures to promote COPD prevention.