FEV1 mediates the effect of major depressive disorder on asthma phenotypes: Mendelian randomization

The causal effect between major depressive disorder (MDD) and asthma phenotypes was rarely evaluated. The objective of our study was to not only assess the potential causal links of MDD on asthma phenotypes, but also the mediating effect of forced expiratory volume in 1 second (FEV1) on asthma phenotypes caused by MDD. By using 2-sample Mendelian randomization (MR), Bayesian weighted MR, and mediation analysis, we explored the potential causal effect of MDD and the mediating effect of FEV1 on asthma phenotypes (childhood asthma, adult asthma, obesity asthma, allergic asthma, and nonallergic asthma) from the genome-wide association studies database. Furthermore, genetic correlation was also evaluated by the analysis of linkage disequilibrium score regression. We additionally performed multivariable MR (MVMR) analyses including body mass index and smoking to evaluate MDD estimates for asthma phenotypes. The results of univariable MR and MVMR analyses supported associations of MDD with adult asthma, obesity asthma, and allergic asthma, and MVMR analysis indicated the potential association of MDD with child asthma and nonallergic asthma. FEV1 indicated a mediated effect of MDD on adult asthma, obesity asthma, allergic asthma, and nonallergic asthma. Our analyses supported associations of MDD with asthma phenotypes. The mediation analysis suggested that FEV1 may mediate part of these associations of MDD on adult asthma, obesity asthma, allergic asthma, and nonallergic asthma.