两样本孟德尔随机化分析循环代谢产物与吉兰-巴雷综合征的因果关系OACSTPCD

Objective To investigate the causal relationship between 417 circulating metabolites and the risk of Guillain-Barré syndrome(GBS)using two sample Mendelian randomization(MR)analysis method.Methods Three genome-wide association studies(GWAS)of circulating metabolites were obtained through the MRC IEU OpenGWAS project,namely"met-a","met-c",and"met-d".The data on single nucleotide polymorphism sites(SNPs)related to GBS was sourced from the FinnGen Consortia database,with the phenotype code"finn-b-G6_GUILBAR".Genetic variation data(SNPs)closely related to circulating metabolites from GWAS was used as instrumental variables(IVs)and a two-sample MR analysis with GBS GWAS data from Finland was conducted.The inverse variance weighted(IVW)method of the random effects model was mainly used,and the results were evaluated based on the odds ratio(OR)and 95%CI of the effect indicators.The leave-one-out method,heterogeneity test,and horizontal gene pleiotropy test were used to verify the stability and reliability of the results.Results There was suggestive evidence for a causal relationship between 5 circulating metabolites and GBS.Among them,the circulating level of creatinine(OR=2.924,95%CI:1.194-7.163,P=0.019),glutamine(OR=1.902,95%CI:1.007-3.592,P=0.048)and isovaleryl carnitine(OR=140.767,95%CI:3.510-5 645.336,P=0.009)were associated with a higher risk of GBS.On the contrary,genetic predicted the circulating level of glucose(OR=0.308,95%CI:0.010-0.981,P=0.046)and X-11491(OR=0.069,95%CI:0.007-0.707,P=0.024)were negatively correlated with the risk of GBS.Conclusion Creatinine,glutamine,isovaleryl carnitine,glucose and X-11491 may have causal relationships with GBS.