Background The 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. Objective In this study, we aimed to investigate this association using univariable Mendelian randomization (UVMR) and multivariable Mendelian randomization (MVMR) analyses. Methods We 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 (FEV 1 ), 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. Results In the UVMR analysis, we showed 23 causal associations, including 21 associations with PEF and 2 with FEV 1 . 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. Conclusions We 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.
Mao et al. (2026) studied this question.