基于孟德尔随机化识别精神分裂症可用药基因

廉坤; 陈怡兰; 张磊; 叶帆; 高云勇; 杨薇

doi:10.16190/j.cnki.45-1211/r.2025.01.011

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

摘要

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。

Abstract:
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.

HTML全文

参考文献(29)

施引文献

资源附件(0)