Mendelian Randomization Evidence for Relationship and Mediation of Educational Attainment on Chronic Obstructive Pulmonary Disease.

Background: Previous epidemiological studies revealed a potential correlation between educational imbalance and chronic obstructive pulmonary disease (COPD) incidence and hospitalization. However, such studies were susceptible to confounding factors and lacked strong causal evidence. The purpose of this study was to utilize Mendelian randomization (MR) to explore the causal relationship between educational attainment (EA) and the onset and hospitalization of COPD, as well as the mediating mechanism of EA on COPD through multivariable MR (MVMR) and two-step MR. Methods: Based on data from genome-wide association studies (GWASs), this study used single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) for EA and COPD. Two-sample MR, MVMR and two-step MR analysis were conducted. The impact of each variable on the outcome was analysed, and the overall mediating effects of smoking, body mass index (BMI) and generalized allergic reactions were assessed. Results: MR analysis suggested that greater EA significantly reduced the incidence (OR = 0.22, 95% CI = 0.12-0.41) and hospitalization (OR = 0.28, 95% CI = 0.18-0.44) of COPD. The MVMR findings suggested that the impact of EA (OR = 0.53, 95% CI = 0.29-0.99) on COPD still existed after adjusting mediators. Combined MVMR and two-step MR analysis revealed that smoking, BMI and allergies mediate 47.9% of the relationship between EA and COPD. Conclusion: High levels of education may have potentially causal protective effect on the onset and hospitalization of COPD. Reducing smoking, obesity and preventing allergic reactions are candidate approaches to prevent COPD, especially in individuals with lower levels of education.