Causal Effect of Physical Activity on Chronic Obstructive Pulmonary Disease: A Two-Sample Mendelian Randomization Study

Abstract

Abstract Background: The relationship between physical activity (PA) and chronic obstructive pulmonary disease (COPD) has remained unclear. In our study, we aimed to assess the causal effect of PA on COPD through a two-sample Mendelian randomization (MR) study. Methods: Genetic instruments associated with PA were derived from a meta-analysis of large-scale genome-wide association studies (GWAS) involving 377,234 individuals of European ancestry from the United Kingdom Biobank and the Atherosclerosis Risk in Communities (ARIC) study. The outcome data were obtained from the FinnGen biobank. To estimate the causal relationship, we employed inverse-variance weighted (IVW) method, MR-Egger, and weighted-median method. Additionally, we conducted Cochran's Q test, MR-Egger regression, Mendelian Randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) and leave-one-out analysis to assess potential pleiotropy effects. Results: Our analysis revealed that genetically predicted strenuous sports or other exercises (SSOE) reduced the risk of COPD (OR=0.06, 95%CI 0.008 - 0.47, P= 0.007) based on the IVW method. However, we did not observe any causal relationship between other phenotypes of PA and COPD. The assessment of heterogeneity and pleiotropy provided further support for the robustness and validity of these MR results. Conclusions: Based on our findings, it can be concluded that SSOE is causally associated with a reduced risk of COPD in individuals of European ancestry. However, we did not observe any causal relationship between other phenotypes of PA and COPD.