Abstract
Chronic obstructive pulmonary disease (COPD) is one of the leading causes of mortality worldwide. However, whether air pollutants can cause COPD remains unknown. Summary data for the genome-wide association study of each phenotype were obtained from the publicly available datasets. Using single-nucleotide polymorphisms as instrumental variables, we performed Mendelian randomization (MR) to assess the relationship among PM2.5, smoking and early-onset COPD. A large-scale genetic analysis is performed to investigate the biological pathways. In MR, exposure to higher PM2.5 increased the risk of early-onset COPD (IVW, OR (95% CI) = 1.63 (1.15, 2.31), p = 5.60E-03) but had no association with later-onset COPD. In addition, cigarettes per day (IVW, OR (95% CI) = 1.71 (1.46, 1.99), p = 1.60E-11) was positively associated with the risk of early-onset COPD, while age of smoking initiation (IVW, OR (95% CI) = 0.39 (0.27, 0.57), p = 1.21E-06) had a negative effect. In addition, two smoking behaviors could be mediators between PM2.5 and early-onset COPD (p < 0.05). Furthermore, 136 significantly enriched biological pathways of PM2.5 potentially causing early-onset COPD were identified in a large-scale genetic analysis. This study provides strong evidence that exposure to higher PM2.5 was causally associated with smoking behavior and early-onset COPD. Smoking behavior acted as a mediator between PM2.5 and early-onset COPD. More attention should be given to people exposed to higher PM2.5 for the prevention of smoking and COPD.