摘要
目的通过两样本双向孟德尔随机化(MR)方法评估儿童哮喘与血清25-羟维生素D[25(OH)D]之间的因果关系。方法利用从公开可用的欧洲人群全基因组关联研究中与血清25(OH)D相关的遗传数据及从英国生物银行中获得与儿童哮喘相关的遗传数据进行双样本双向MR分析。采用逆方差加权法(IVW)、一般模型、加权模型、加权中值法、MR Egger方法进行分析,并进行异质性检验,敏感性分析及多效性分析。结果MR分析结果表明,血清25(OH)D水平与儿童哮喘存在因果关系(IVW OR:0.997,95%CI:0.995~0.999,P=0.018),儿童哮喘与血清25(OH)D水平不存在因果关系(IVW OR:1.627,95%CI:0.244~10.871,P=0.615)。在血清25(OH)D水平对儿童哮喘的MR分析中,工具变量不存在水平多效性及异质性。使用留一法(leave-one-out法)和可视化散点图进行的敏感性分析发现,MR分析结果稳健。在儿童哮喘对血清25(OH)D水平的MR分析中,工具变量不存在水平多效性,存在异质性。使用留一法和可视化散点图进行的敏感性分析发现,MR分析结果不稳健。结论双样本MR分析表明了一种单向因果关系,即血清25(OH)D水平越低,患儿童哮喘的风险越大。然而,儿童哮喘似乎并不影响血清25(OH)D水平。
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.
作者
纪展鹏
魏兵
JI Zhanpeng;WEI Bing(Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China)
出处
《中国中西医结合儿科学》
2024年第2期148-154,共7页
Chinese Pediatrics of Integrated Traditional and Western Medicine
基金
辽宁省科学技术计划项目(2021HJ2/10300060)。
关键词
哮喘
维生素D
孟德尔随机化
儿童
Asthma
Vitamin D
Mendelian randomization
Children