microRNAs与子宫内膜异位症相关性的双样本孟德尔随机化研究OA

Objective:To investigate the potential causal relationship between circulat-ing microRNAs(miRNAs)and the risk of endometriosis(EMs)using a two-sample Mendelian randomization(MR)approach.Methods:This study integrated miRNA expression quantitative trait loci(miR-eQTL)data and genome-wide association study(GWAS)summary statistics for endometriosis.Inverse-variance weighted(IVW)and weighted median methods were employed for MR analyses to systematically assess the causal relationship between miRNAs and EMs.MiRNet 2.0 and miRTarBase databases were utilized to predict target genes of significantly as-sociated miRNAs,followed by functional enrichment analysis.Results:Genetically predicted higher levels of miR-130a-3p were significantly associated with an increased overall risk of EMs(Weighted median:OR=1.263,95%CI:1.142 to 1.398,FDR-corrected P=0.010;IVW:OR=1.202,95%CI:1.125 to 1.285,FDR-corrected P=8.83×10-5).Genetically predicted high-er levels of miR-30b-5p and miR-30d-5p exhibited protective effects,particularly associated with a reduced risk of deeply infiltrating endometriosis(DIE)in the rectovaginal septum.Gene Ontology(GO)functional enrichment analysis indicated that the target genes of these three miRNAs were significantly enriched in pathways related to miRNA metabolic processes and transcriptional regulation.Conclusion:This study suggests that genetically predicted higher ex-pression of miR-130a-3p is a potential risk factor for EMs,while higher expression of miR-30b-5p and miR-30d-5p may confer protection.These miRNAs demonstrate potential causal relation-ships with EMs pathogenesis,providing candidate circulating biomarkers for the clinical diagno-sis and treatment of EMs.