柔肝愈偏饮潜在作用靶点与偏头痛的孟德尔随机化研究OA

Objective To study predicted the core targets of Rougan Yupian drink in the treatment of migraine based on Network Pharmacology.The two-sample Mendelian randomization(MR)method was adopted to evaluate the genetic causal associations between the key targets and migraine.Methods On the basis of the 15 core targets,expression quantitative trait locus(eQTL)data acquired from the eQTLGen consortium were taken as exposure variables,and migraine GWAS data extracted from the IEU Open GWAS database served as outcome variables.Significantly correlated and mutually independent single-nucleotide polymorphisms(SNPs)(F>10)were screened,with cis-eQTLs prioritized.The inverse variance weighted(IVW)method was adopted as the primary analytical approach,supplemented by the weighted median method and MR-Egger regression.Cochran's Q test and MR-Egger intercept were used to assess heterogeneity and horizontal pleiotropy,the Steiger test was applied to determine causal direction,and Bonferroni correction was performed.Results The IVW analysis revealed that AKT1 expression level was positively associated with migraine risk(OR=1.076,95%CI:1.038‒1.115,P=5.13×10-5),indicating that elevated AKT1 expression may correlate with increased migraine risk.BCL2 also showed a positive association(OR=1.103,P=0.043).ESR1(OR=0.912,P=0.035),MMP9(OR=0.955,P=0.022)and IL6(OR=0.886,P=0.029)tended to be associated with reduced migraine risk.Consistent effect directions were observed across multiple MR methods.After Bonferroni correction,only AKT1 remained statistically significant.Conclusion There was a genetic causal association between AKT1 expression and migraine risk,indicating that AKT1 may serve as one of the crucial therapeutic targets.These findings provided genetic evidence supporting the hypothesis that Rougan Yupian drink has therapeutic effects via relevant molecular pathways.Nevertheless,the specific mechanisms remained to be further verified in subsequent studies.