Publication date: May 21, 2025

The mechanistic relationship between respiratory disorders and brain function remains poorly understood, despite growing evidence of cognitive and neurological manifestations in respiratory diseases. We aim to identify whether specific brain network connectivity patterns causally influence respiratory disease susceptibility, while respiratory conditions might reciprocally affect brain network architecture. We performed bidirectional Mendelian randomization analyses using genome-wide association studies (GWAS) of brain network connectivity from UK Biobank resting-state functional MRI data (N=31,453) and GWAS data from ten major respiratory conditions: chronic obstructive pulmonary disease (COPD), asthma, idiopathic pulmonary fibrosis (IPF), sleep apnea syndrome (SAS), lung squamous carcinoma (LUSC), lung adenocarcinoma (LUAD), small cell lung carcinoma (SCLC), hospitalized COVID-19, very severe COVID-19, and bronchiectasis. Five MR methods, inverse variance weighted (IVW) with multiplicative random-effect model, weighted median, weighted mode, MR Egger, and MR-robust adjusted profile score (MR-RAPS) were employed to ensure causal inference. In forward analysis, five respiratory disorders – asthma, IPF, SAS, LUSC, and very severe COVID-19 – showed significant causal associations (p

Semantics

Original Article