基于孟德尔随机化的肠道菌群与水痘发生关联性分析  

Analysis on association between gut microbiota and varicella based on Mendelian randomization

作　　者：陈哲 王燕[1] 张国清[1] 张新新 郑鲁 张咪 司侠[1] 梁玉民[1] CHEN Zhe;WANG Yan;ZHANG Guo-qing;ZHANG Xin-xin;ZHENG Lu;ZHANG Mi;SI Xia;LIANG Yu-min(Immunization Planning Section,Jining City Center for Disease Control and Prevention,Shandong 272000,China)

机构地区：[1]济宁市疾病预防控制中心免疫规划科,山东272000

出　　处：《预防医学论坛》2024年第12期911-915,共5页Preventive Medicine Tribune

基　　金：山东省医药卫生科技项目(202312051330)。

摘　　要：目的采用孟德尔随机化(MR)方法探索肠道菌群(GM)与水痘发生的关联性,分析二者可能存在的共同遗传机制,为水痘的预防和早期干预提供依据。方法2023年12月采用公共数据库MiBioGen研究的GM全基因组关联研究(GWAS)数据和芬兰数据库水痘GWAS数据,进行双向MR研究,分析GM与水痘发生的关联性。用逆方差加权法(IVW)作为MR方法的主要分析方法,加权中位数法(WME)和MR-Egger进行补充分析,并使用异质性检验、多效性检验和留一法进行敏感性分析,验证结果的稳定性和可靠性。结果IVW结果显示肠杆菌属(OR=0.73,95%CI:0.54~1.00,P=0.04)是水痘发生的保护因素,疣微菌群(OR=1.64,95%CI:1.16~2.33,P=0.006)、疣微菌目(OR=1.64,95%CI:1.16~2.33,P=0.006)、疣微菌门(OR=1.47,95%CI:1.06~2.06,P=0.02)、疣微菌纲(OR=1.61,95%CI:1.00~2.62,P=0.006)、普雷沃特氏菌属7(OR=1.29,95%CI:1.03~1.59,P=0.02)、阿克曼氏菌属(OR=1.62,95%CI:0.98~2.65,P=0.06)是水痘发生的危险因素。敏感性分析显示单核苷酸多态性(SNP)之间不存在异质性,且本研究中不存在水平多效性。留一法分析证实,无单个SNP对整体的结果有较大影响。结论基于MR的关联性分析表明,肠杆菌属是水痘发生的保护因素,疣微菌群、疣微菌目、疣微菌门、疣微菌纲、普雷沃特氏菌属7和阿克曼氏菌属是水痘发生的危险因素。Objective To explore the association between gut microbiota(GM)and varicella using Mendelian randomization(MR)method,and to analyze the possible common genetic mechanisms between them,so as to provide a basis for the prevention and early intervention of varicella.Methods In December 2023,a bidirectional Mendelian randomization(MR)study was conducted to analyze the association between gut microbiota(GM)and varicella using GM genome-wide association study(GWAS)data from the public database MiBioGen and varicella GWAS data from a Finnish database.Inverse-variance weighted(IVW)method was employed as the primary analytical approach for MR,supplemented by weighted median estimator(WME)and MR-Egger.Heterogeneity tests,pleiotropy tests,and leave-one-out analysis were performed for sensitivity analysis to verify the stability and reliability of the results.Results The IVW results indicated that genus.Intestinibacter(OR=0.73,95%CI:0.54-1.00,P=0.04)was a protective factor against the occurrence of varicella,while family.Verrucomicrobiaceae(OR=1.64,95%CI:1.16-2.33,P=0.006),order.Verrucomicrobiales(OR=1.64,95%CI:1.16-2.33,P=0.006),phylum.Verrucomicrobia(OR=1.47,95%CI:1.06-2.06,P=0.02),class.Verrucomicrobiae(OR=1.61,95%CI:1.00-2.62,P=0.006),genus.Prevotella7(OR=1.29,95%CI:1.03-1.59,P=0.02),and genus.Akkermansia(OR=1.62,95%CI:0.98-2.65,P=0.06)were risk factors for varicella.Sensitivity analysis revealed no heterogeneity among single nucleotide polymorphisms(SNPs)and no horizontal pleiotropy in this study.The leave-one-out analysis confirmed that no single SNP had a significant impact on the overall results.Conclusion The association analysis based on MR showed that,genus Intestinibacter is a protective factor for the occurrence of varicella,family.Verrucomicrobiaceae,order.Verrucomicrobiales,phylum.Verrucomicrobia,class.Verrucomicrobiae,genus.Prevotella7and genus.Akkermansia are risk factors for the occurrence of varicella.

关 键 词：肠道菌群 水痘 孟德尔随机化 关联性分析 

分 类 号：R183.3[医药卫生—流行病学]