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

BackgroundThe cross-organ regulatory relationship between the lung and brain has been suggested. However, the causal associations between lung function and brain neuronal activity remain unclear.ObjectiveIn this study, we aimed to investigate this association using univariable Mendelian randomization (UVMR) and multivariable Mendelian randomization (MVMR) analyses.MethodsWe utilized summary data from genome-wide association studies of European ancestry for three lung function indicators (n = 400,102), including peak expiratory flow (PEF), forced expiratory volume in 1 s (FEV₁), and forced vital capacity, and 68 brain regional neuronal activity amplitude traits (NAATs) (n = 34,691). The inverse-variance weighted method was employed to obtain main causal estimates. Sensitivity analyses were performed.ResultsIn the UVMR analysis, we showed 23 causal associations, including 21 associations with PEF and 2 with FEV₁. The MVMR analysis revealed eight causal associations between PEF and NAATs. These associations were observed across multiple regions, mainly in the precuneus, middle and inferior frontal gyrus, superior and middle occipital gyrus, superior parietal gyrus, inferior parietal lobule, postcentral gyrus, and crus I and II of the cerebellar hemispheres. Among these, causal associations between PEF and the NAAT of the middle occipital gyrus and precuneus (β = -0.146, P = 0.024) and the NAAT of the middle frontal gyrus and crus I and II of the cerebellar hemispheres (β = -0.139, P = 0.024) were observed.ConclusionsWe demonstrated the genetically predicted causal effects of PEF on brain neuronal activity. Closely monitoring PEF reductions in patients with lung disease may be critical for promptly detecting abnormal brain function.