Abstract: Objective To evaluate the causal relationship between childhood asthma and serum 25-hydroxyvitamin D［25(OH)D］ by two-sample bidirectional Mendelian randomization.Methods A two-sample bidirectional MR analysis was performed using pool-level genetic data associated with serum 25(OH)D from publicly available European population-wide association studies and pool-level genetic data associated with childhood asthma from UK Biobank.Inverse variance weighted (IVW) method,simple mode method,weighted mode,weighted median method,and MR Egger method were used for analysis,and heterogeneity test,sensitivity analysis and pleiotropic analysis were conducted.Results The results of MR analysis showed that there was a causal relationship between serum 25(OH)D level and childhood asthma(IVW OR:0.997,95%CI:0.995,0.999,P=0.018).There was no causal relationship between childhood asthma and serum 25(OH)D level(IVW OR:1.627,95%CI:0.244,10.871,P=0.615).In MR analysis of serum 25(OH)D level in children with asthma,there was no horizontal pleiotropy or heterogeneity of instrumental variables.Sensitivity analysis using the leave-one-out method and visual scatter plots showed robust MR analysis results.In reverse MR analysis,there was no horizontal pleiotropy of instrumental variables,but there was heterogeneity.Sensitivity analysis using the leave-one-out method and visual scatter plots found that MR analysis results were not robust.Conclusion Two-sample MR analysis shows a unidirectional causal relationship,that is,the lower the serum 25(OH)D level,the greater the risk of childhood asthma.However,childhood asthma does not appear to affect serum 25(OH)D levels.

Key words:

Asthma, Vitamin D, Mendelian randomization, Children