Causal association between chronic obstructive pulmonary disease and brain cortical structure: A Mendelian...

Observational studies have demonstrated an association between chronic obstructive pulmonary disease (COPD) and structural changes in the brain cortex. However, the causality remains undetermined. This study aims to establish the causal impact of COPD and lung function on brain cortical structure (surface area (SA) and thickness (TH)).

Using Mendelian randomization (MR) analysis. Data from Genome-wide association studies (GWAS) of European ancestry were used. The inverse variance weighted (IVW) method was employed as the primary approach and sensitivity analyses were conducted to examine the robustness of the results.

On the global scale, FVC was significantly positively correlated with brain cortical SA (β_SA = 1644.01 mm², P = 0.01). On a regional scale after Bonferroni correction, forced vital capacity (FVC) was found to be significantly positively correlated with the SA of the medial orbitofrontal without global weighted (β_SA = 30.94 mm², P = 0.00035) and the SA of the middle temporal without global weighted (β_SA = 55.37 mm², P = 0.0003). Forced expiratory volume in one second (FEV1) was significantly negatively correlated with the SA of the frontal pole with global weighted (β_SA = -3.40 mm², P = 0.0003). There were also suggestive evidence showing nominal associations of COPD and lung function with certain brain cortical structures.

These findings suggest that COPD and lung function affect brain cortical structure, indicating the presence of a lung-brain axis.