Causal association between sleep phenotypes and susceptibility to childhood asthma: A two-sample Mendelian randomization study.

OBJECTIVE: This study applied two-sample Mendelian randomization (MR) to elucidate causal relationships between sleep-related phenotypes and childhood asthma risk. METHODS: Instrumental variables for daytime napping, sleep disorders, chronotype, and fatigue were selected from European ancestry genome-wide association studies. Causal estimates were primarily derived using inverse-variance weighting (IVW), supplemented by sensitivity analyses including MR-Egger and MR-PRESSO. Instrument validity, heterogeneity, pleiotropy, and directionality were rigorously evaluated. RESULTS: IVW results demonstrated that genetic susceptibility to daytime napping (OR = 1.76; 95% CI: 1.07-2.88; p < .05), sleep disorders (OR = 1.35; 95% CI: 1.12-1.61; p < .05), and frequent fatigue (OR = 2.94; 95% CI: 1.61-5.38; p < .05) significantly increased asthma risk, whereas morning chronotype was protective (OR = 0.76; 95% CI: 0.61-0.98; p = .015). Sensitivity analyses supported these findings, with no evidence of pleiotropy or reverse causation. CONCLUSIONS: These results suggest that sleep behaviors causally influence childhood asthma risk and may represent modifiable targets for prevention and management.