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.