阿尔兹海默症与哮喘的因果关系:一项两样本双向孟德尔随机化研究

Causality between Alzheimer's disease and asthma:a two-sample Mendelian randomization study

目的:采用两样本孟德尔随机化法(Mendelian randomization,MR)探究阿尔兹海默症(Alzheimer's disease,AD)与哮喘的双向因果关系。方法:基于欧洲人群的全基因组关联研究(GWAS)数据,采用逆方差加权法(Inverse Variance Weighted,IVW)进行主要分析,辅以MR-Egger、加权中位数和加权模式等方法,评估AD与哮喘的关联。结果:分别有15个和103个单核苷酸多态性(Single Nucleotide Polymorphism,SNP)被纳入作为AD和哮喘的工具变量。结果表明,在欧洲人群中,AD是哮喘发病危险因素(IVW:OR=0.996,95%CI=0.994~0.999,P=0.008);哮喘与AD的发病无关(IVW:OR=0.868,95%CI=0.509~1.481,P=0.604)。Cochran’s Q检验表明纳入的工具变量之间不具有异质性,MRPRESSO检验显示不存在水平多效性,留一法也未发现离群SNP。结论:基于欧洲人群遗传数据的MR研究表明,AD是哮喘发病的风险因素。这一发现有助于深入了解AD和哮喘的关联,为相关疾病的中医药临床防治措施提供了重要的基础。

Objective:To explore the bidrectional causal relationship between Alzheimer's disease(AD)and asthma using a twosample Mendelian randomization(MR)study.Methods:The association between AD and asthma was assessed using Inverse Variance Weighted(IVW),MR-Egger,weighted median,and weighted mode,based on the European genome-wide association study(GWAS)data.Results:Finally,15 and 103 Single Nucleotide Polymorphism(SNP)were included as instrumental variables for AD and asthma,respectively.The results showed that AD was a risk factor for asthma in the European population(IVW:OR=0.996,95%CI=0.994~0.999,P=0.008);asthma was not associated with the onset of AD(IVW:OR=0.868,95%CI=0.509~1.481,P=0.604).The Cochran's Q test indicated no heterogeneity among the included instrumental variables.The MR-PRESSO test showed no horizontal pleiotropy,and no outlier SNP was found by the leave-one-out method.Conclusion:MR studies based on genetic data from European populations suggest that AD is a risk factor for asthma onset.This finding provides an insight into the association of AD and asthma,and provides an important basis for TCM clinical prevention and treatment measures for related diseases.