Related Experiment Video
Updated: Jun 24, 2025
Author Spotlight: Finding New Therapeutic Targets for Malignant Peripheral Nerve Sheath Tumor Through Genome-Scale shRNA Screens
Published on: August 25, 2023
Identifying therapeutic target genes for migraine by systematic druggable genome-wide Mendelian randomization
Chengcheng Zhang1, Yiwei He2, Lu Liu3
1Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing Key Laboratory of Acupuncture Neuromodulation, No. 23, Meishuguan Houjie, Beijing, 100010, China.
Background:
Currently, the treatment and prevention of migraine remain highly challenging. Mendelian randomization (MR) has been widely used to explore novel therapeutic targets. Therefore, we performed a systematic druggable genome-wide MR to explore the potential therapeutic targets for migraine.
Methods:
We obtained data on druggable genes and screened for genes within brain expression quantitative trait locis (eQTLs) and blood eQTLs, which were then subjected to two-sample MR analysis and colocalization analysis with migraine genome-wide association studies data to identify genes highly associated with migraine. In addition, phenome-wide research, enrichment analysis, protein network construction, drug prediction, and molecular docking were performed to provide valuable guidance for the development of more effective and targeted therapeutic drugs.
Results:
We identified 21 druggable genes significantly associated with migraine (BRPF3, CBFB, CDK4, CHD4, DDIT4, EP300, EPHA5, FGFRL1, FXN, HMGCR, HVCN1, KCNK5, MRGPRE, NLGN2, NR1D1, PLXNB1, TGFB1, TGFB3, THRA, TLN1 and TP53), two of which were significant in both blood and brain (HMGCR and TGFB3). The results of phenome-wide research showed that HMGCR was highly correlated with low-density lipoprotein, and TGFB3 was primarily associated with insulin-like growth factor 1 levels.
Conclusions:
This study utilized MR and colocalization analysis to identify 21 potential drug targets for migraine, two of which were significant in both blood and brain. These findings provide promising leads for more effective migraine treatments, potentially reducing drug development costs.
