Mapping the lung-brain axis: Causal relationships between brain network connectivity and respiratory disorders

Area of Science:

• Neuroscience
• Genetics
• Respiratory Medicine

Background:

• The connection between respiratory disorders and brain function is not well understood.
• Growing evidence links respiratory diseases to cognitive and neurological issues.
• The bidirectional relationship between brain networks and respiratory conditions needs clarification.

Purpose of the Study:

• To investigate if brain network connectivity causally influences susceptibility to respiratory diseases.
• To explore if respiratory conditions reciprocally impact brain network architecture.
• To identify specific brain networks and respiratory conditions with causal links.

Main Methods:

• Bidirectional Mendelian randomization (MR) analyses were performed.
• Genome-wide association studies (GWAS) data from UK Biobank rs-fMRI (N=31,453) and ten respiratory conditions were used.
• Five MR methods (IVW, weighted median, weighted mode, MR Egger, MR-RAPS) ensured robust causal inference.

Main Results:

• Forward analysis: Asthma, IPF, SAS, LUSC, and severe COVID-19 showed causal links to 11 brain network phenotypes.
• Reverse analysis: Twelve brain networks were genetically associated with eight respiratory conditions (COPD, asthma, IPF, SAS, LUSC, SCLC, COVID-19).
• Affected networks included executive, subcortical-cerebellum, motor, limbic, attention, salience, visual, and default mode networks.

Conclusions:

• Preliminary genetic evidence suggests causal relationships between brain network connectivity and respiratory disorders.
• Findings contribute to understanding the lung-brain axis.
• Disease-specific network alterations offer insights but require clinical validation for therapeutic applications.