使用镇静催眠药与颅内未破裂动脉瘤发生风险的遗传因果关系:一项孟德尔随机化研究OA

Objective To investigate the genetic causal relationship between the use of sedative-hypnotics and intracranial aneurysms(IAs),including its different subtypes.Methods A two-sample Mendelian randomization(MR)design was employed.Single nucleotide polymorphisms(SNPs)associated with sedative-hypnotic use,derived from a genome-wide association study(GWAS),were selected as genetic instrumental variables.Genetic data for IAs were obtained from the International Stroke Genetics Consortium,including data from individuals of European ancestry.The inverse variance weighted(IVW)method was used as the primary analysis.Five MR methods were employed to analyze the causal relationship between sedative-hypnotic use and IAs,unruptured intracranial aneurysms(UIA),and aneurysmal subarachnoid hemorrhage(aSAH).Sensitivity analyses were conducted using MR-Egger regression,the MR-PRESSO test,and the leave-one-out method.The F-statistic was used to evaluate the validity of the instrumental variables.Results A total of 30 valid SNPs associated with sedative-hypnotic use were identified,all with F-statistics>10,indicating no evidence of weak instrumental variables bias.The IVW analysis results showed a causal relationship between sedative-hypnotic use and an increased risk of UIA[OR(95%CI)=1.669(1.012-2.752),P<0.05].The other four MR analysis methods showed effect directions consistent with IVW,all indicating that the use of sedative-hypnotic drugs increases the risk of UIA.However,no genetic causal relationship was found between sedative-hypnotic use and IAs or aSAH(P>0.05).Cochran's Q test showed no significant heterogeneity,MR-Egger regression indicated no significant horizontal pleiotropy,and leave-one-out analysis as well as MR-PRESSO confirmed the robustness of the results.Conclusion The use of sedative-hypnotics increases the risk of developing UIA.