Objective To explore the levels of serum hsa-miR3173-5p and hsa-miR-4297 and their feasibility as the diagnostic markers in cardiogenic stroke.Methods GEO database integration analysis screened out possible cardiogenic stroke-specific miRNAs(hsa-miR3173-5p and hsa-miR-4297),verified the risk role of the two miRNAs in the development of cardiogenic stroke by Mendelian randomization and colocalization analysis,and their target genes in the miRNA-mRNA regulatory network were enriched to search for related pathways.A total of 103 patients newly diagnosed with ischemic stroke in the emergency department from March 2022 to January 2023 were included,among which 22 cases were cardiogenic stroke(case group)and 81 were non-cardiogenic stroke(control group).The expression levels of serum hsa-miR3173-5p and hsa-miR-4297 were detected by real-time quantitative polymerase chain reaction,and their correlation with cardiogenic stroke was analyzed by multivariable logistic regression.The predictive value was evaluated using the receiver operating characteristic(ROC)curve.Results Mendelian randomization analysis suggested that genetically predicted increased expression of hsa-miR3173-5p and hsa-miR-4297 in circulating blood increased the risk of cardiogenic stroke by 46%and 70%respectively.Colocalization analysis suggested that the expression of hsa-miR3173-5p and hsa-miR-4297 in circulating blood has a 95%and 86%probability of shared genetic variation with cardiogenic stroke,respectively.The expression levels of serum hsa-miR3173-5p and hsa-miR-4297 in the case group were significantly higher than in the control group(P<0.05),and hsa-miR3173-5p(OR=6.30,95%CI 1.79~22.14,P=0.004)and hsa-miR-4297(OR=12.38,95%CI 1.97~77.72,P=0.007)were significantly associated with cardiogenic stroke.The area under the ROC curve(AUC)for hsa-miR3173-5p and hsa-miR-4297 were 0.705 and 0.624 respectively,and the AUC of the combined analysis of hsa-miR3173-5p and hsa-miR-4297 with atrial fibrillation is 0.842.Conclusion The expression levels of hsa-miR3173-5p and hsa-miR-4297 are closely related to cardiogenic stroke,and are promising as diagnostic markers for cardiogenic stroke.