Smoking and asthma mediate the protective effect of educational attainment on chronic obstructive pulmonary disease risk: a mediation Mendelian randomization analysis.

BACKGROUND

Clinical observational studies have shown an association between educational attainment and a lower incidence of Chronic Obstructive Pulmonary Disease (COPD). However, strong evidence for a causal relationship remains lacking.

METHODS

Genome-wide association data for years of schooling, cognitive performance, intelligence, COPD, and COPD-related risk factors such as smoking and asthma were obtained from public databases. We conducted two-sample Mendelian randomization (MR) analyses to assess the causal relationships between years of schooling, cognitive performance, intelligence, and the risk of developing COPD. Sensitivity analyses using MR-Egger and MR-PRESSO were performed to detect and correct for pleiotropy. Multivariable Mendelian randomization analysis was used to identify potential mediators.

RESULTS

Longer years of schooling (OR = 0.537, 95% CI: 0.474-0.608, P = 9.63E-23), higher cognitive performance (OR = 0.793, 95% CI: 0.702-0.895, P = 1.78E-04), and intelligence (OR = 0.813, 95% CI: 0.720-0.919, P = 8.81E-04) were causally associated with a reduced risk of COPD. Longer years of schooling were identified as an independent protective factor for COPD risk (OR = 0.600, 95% CI: 0.472 - 0.762, P = 2.85E-05). Smoking initiation and asthma were identified as mediating factors in the causal relationship between years of schooling and COPD risk. In the reduction of the COPD risk by years of schooling, the mediating effects of smoking initiation and asthma accounted for 32.8% and 6.9% respectively.

CONCLUSION

These findings provide support for the causal impact of educational attainment on the occurrence of COPD, with a significant portion of this causal effect being mediated through modifiable risk factors. On the premise of controlling socioeconomic - status - related confounders, an increase in educational attainment may provide multi-level intervention targets for COPD prevention through intervenable pathways such as improving health behaviors and environmental exposure.