基于孟德尔随机化识别精神分裂症可用药基因  

Identification of druggable genes for schizophrenia based on Mendelian randomization

作　　者：廉坤[1] 陈怡兰 张磊[2] 叶帆 高云勇 杨薇[2] LIAN Kun;CHEN Yilan;ZHANG Lei;YE Fan;GAO Yunyong;YANG Wei(Department of Neurosurgery,the Second Affiliated Hospital of Kunming Medical University,Kunming 650101,China;Department of Psychiatry,the Second People’s Hospital of Yuxi/Yuxi Hospital Affiliated to Kunming University of Science and Technology,Yuxi 653100,China)

机构地区：[1]昆明医科大学第二附属医院神经外科,昆明650101 [2]玉溪市第二人民医院,昆明理工大学附属玉溪医院精神科,玉溪653100

出　　处：《广西医科大学学报》2025年第1期87-92,共6页Journal of Guangxi Medical University

基　　金：昆明理工大学医学联合专项(No.KUST-YX2022002)。

摘　　要：目的:寻找精神分裂症(SCZ)潜在的药物治疗靶点基因。方法:从eQTLGen数据库中获取可用药基因,并将其与SCZ的全基因组关联研究(GWAS)数据进行整合。采用两样本孟德尔随机化(MR)和共定位分析方法,计算可用药基因的表达数量性状位点(eQTL)与SCZ之间存在共同致病变异的关联。最后采用基于汇总数据的MR(SMR)对共定位的阳性结果进行筛选和验证。结果:SMR鉴定出6个与SCZ显著关联的潜在可用药基因:NMB、IK、FGFR1、SERPING1、EDEM2和CTSS。结论:通过MR、共定位和SMR验证确定了6个可作为SCZ潜在治疗靶点的可用药基因,这些发现为SCZ治疗的发展提供了新的见解。Objective:To find the potential therapeutic targetgenes of schizophrenia(SCZ).Methods:Druggable genes were obtained from eQTLGen database and integrated with genome-wide association studies(GWAS)data of SCZ.Two-sample Mendelian randomization(MR)and colocalization analysis were used to calculate the association between expression quantitative trait loci(eQTL)of druggable genes and the presence of common pathogenic variants in SCZ.Finally,summary-data-based MR(SMR)was used to further validate the positive results of colocalization.Results:SMR identified six potentially druggable genes that were significantly associated with SCZ:NMB,IK,FGFR1,SERPING1,EDEM2 and CTSS.Conclusion:Six druggable genes that can be potential therapeutic targets for SCZ are identified by MR,colocalization and SMR validation,and these findings provide new insights into the development of SCZ therapy.

关 键 词：精神分裂症 可用药基因 孟德尔随机化 共定位分析 

分 类 号：R749.3[医药卫生—神经病学与精神病学]