Peak expiratory flow causally affects brain neuronal activity: A Mendelian randomization study.

Area of Science:

• Neuroscience
• Pulmonology
• Genetics

Background:

• The lung-brain axis suggests cross-organ regulatory relationships.
• Causal links between lung function and brain neuronal activity require clarification.

Purpose of the Study:

• To investigate the causal association between lung function and brain regional neuronal activity amplitude traits (NAATs).
• Utilized Mendelian randomization to explore genetic links between lung function and brain activity.

Main Methods:

• Employed univariable (UVMR) and multivariable Mendelian randomization (MVMR) analyses.
• Utilized genome-wide association study summary data for lung function indicators (n=400,102) and brain NAATs (n=34,691).
• Applied the inverse-variance weighted method for causal estimates and conducted sensitivity analyses.

Main Results:

• Identified 23 causal associations in UVMR, including 21 for peak expiratory flow (PEF) and 2 for forced expiratory volume in 1 second (FEV1).
• MVMR revealed eight causal associations between PEF and NAATs across various brain regions.
• Significant associations were found between PEF and neuronal activity in the middle occipital gyrus, precuneus, middle frontal gyrus, and cerebellum.

Conclusions:

• Demonstrated genetically predicted causal effects of PEF on brain neuronal activity.
• Reduced PEF is associated with altered neuronal activity in specific brain regions.
• Monitoring PEF may be crucial for early detection of brain dysfunction in lung disease patients.