Objective This study aimed to explore the causal relationship between gut microbiota and aplastic anemia(AA)using a two-sample Mendelian randomization(MR)approach.Methods The genome-wide association significance level of the gut microbiota genetic data was set at P<1×10-5 and r2=0.001 and clumping distance=10 000 kb to eliminate linkage disequilibrium(LD).The remaining strong and independent single nucleotide polymorphisms(SNP)were used as genetic instrumental variants(IV)for MR analysis.The sensitivity analyses included the MR-PRESSO global test,the MR-Egger intercept test,the Cochran's Q test was and the leave-one-out method.Results A total of eight gut microbiota species with 109 SNP were included in the study.The results showed that phylum Bacteroidetes,class Bacteroidia,order Bacteroidales,genus Anaerotruncus,genus Eubacterium hallii group,genus Family XIII UCG001 and genus Intestinibacter were positively correlated with AA risk(ORIVW=1.343,95%CI 1.030～1.752,PIVW=0.029;ORIVW=1.386,95%CI 1.094～1.757,PIVW=0.007;ORIVW=1.386,95%CI 1.094～1.757,PIVW=0.007;ORIVW=1.365,95%CI 1.036～1.799,PIVW=0.027;ORIVW=1.224,95%CI 1.008～1.488,PIVW=0.042;ORIVW=1.399,95%CI 1.085～1.804,PIVW=0.010;ORIVW=1.244,95%CI 1.034～1.497,PIVW=0.021).In contrast,genus Parasutterella was negatively associated with the risk of AA(ORIVW=0.835,95%CI 0.703～0.992,PIVW=0.041).Reverse MR study did not observe a causal effect of AA on gut microbiota.Conclusion Two-sample MR method confirmed the potential causal role of gut microbiota in AA.The underlying mechanism of the causal link between the two needs to be further explored in further studies.
Gut microbiotaAplastic anemiaMendelian randomizationSingle nucleotide polymorphismsGenetic instrumental variants
NETL
NSTL
万方数据
