目的 采用两样本孟德尔随机化法(Mendelian randomization，MR)分析肠道菌群与缺血性脑卒中(ischemic stroke，IS)发病风险的因果关联。方法 肠道菌群汇总数据来自MiBio-Gen联盟进行的全基因组关联荟萃分析资料;IS数据来自IEU Open GWAS数据库。采用逆方差加权法、MR-Egger法、加权中值法、简单众数法及加权众数法研究肠道菌群与IS之间的因果关联。以OR(95％CI)值评价肠道菌群对IS发病风险的因果关系。采用MR-PRESS O和MR-Egger回归分析检验多效性，Cochran's Q检验评估工具变量的异质性。"留一法"分析评估每个单核苷酸(single nucleotide polymorphism，SNPs)对结局的影响。结果 从门、纲、目、科、属五个水平对211种肠道菌群与IS进行因果关联性分析结果表明，Lentisphaerae、Clostridia、Clostridiales、Clostridiaceael、Barnesiella、Intestinimonas、Lachnospiraceae NK4A136 group 及 Lachnospiraceae FCS020 group与IS的发病呈负相关，而Allisonella、Paraprevotella及Streptococcus与IS的发病呈正相关。经过Bonferroni方法进行多重校正后，发现Clostridiaceael与IS具有显著因果关系。MR-PRESSO和MR-Egger回归分析显示不存在多效性(P＞0。05)，Cochran's Q检验结果表明不存在异质性(P＞0。05)，"留一法"分析显示结果稳定。结论 肠道菌群与IS的发病存在因果关系，Lentisphaerae、Clostridia、Clostridiales、Clostridiaceae1、Barnesiella、Intestinimonas、Lachnospiraceae NK4A136 group 及 Lachnospiraceae FCS020 group 可能是IS的保护因素，而Allisonella、Paraprevotella及Streptococcus可能是IS的危险因素，其中Clostridi-aceael 能显著降低IS的发病风险。
Causal association between gut microbiota and ischemic stroke based on Mendelian randomization study
Objective To analyze the causal association between gut microbiota and risk of ischemic stroke(IS)using two-sample Mendelian randomization(MR).Methods The aggregate data on gut microbiota were obtained from genome-wide association meta-analyses conducted by the MiBio-Gen Consortium,while IS data were sourced from the IEU Open GWAS database.The causal association between gut microbiota and IS was explored using various statistical methods in-cluding Inverse-variance Weighted,MR-Egger method,MR-Egger,Weighted Median Estimator,Simple Mode and Weighted Mode.The OR(95％CI)value was utilized to assess the causal relationship between gut microbiota and the risk of IS.Additionally,MR-PRESSO and MR-Egger regression analyses were performed to examine pleiotropy,while Co-chran's Q test was used to evaluate instrumental variable heterogeneity."Leave-one-out"analysis was conducted to assess the impact of each SNPs on the outcome.Results We analyzed the causal relationship between 211 gut microbiota and IS at five levels:phylum,class,order,family and genus.The results showed that Lentisphaerae,Clostridia,Clostridiales,Clostridiaceael,Barnesiella,Intestinimonas,Lachnospiraceae NK4A136 group and Lachnospiraceae FCS020 group were negatively correlated with the incidence of IS.Allisonella,Paraprevotella and Streptococcus were positively correlated with the incidence of IS.After multiple correction by Bonferroni method,it was found that Clostridiaceael had a signific-ant causal relationship with IS.MR-PRESSO and MR-Egger regression analysis showed that there was no pleiotropy(P＞0.05).Cochran's Q test showed no heterogeneity(P＞0.05).The results of"Leave-one-out"analysis were stable.Conclusion There is a causal relationship between gut microbiota and the onset of IS;Lentisphaerae,Clostridia,Clostridiales,Clostridiaceael,Barnesiella,Intestinimonas,Lachnospiraceae NK4A136 group and Lachnospiraceae FCS020 group may be protective factors of IS.Allisonella,Paraprevotella and Streptococcus may be risk factors for IS.Clostridiaceael can significantly reduce the risk of IS.
万方数据
维普
