Identifying potential drug targets for tourette syndrome: a Mendelian randomization study based on druggable genes
Abstract Background Tourette syndrome (TS) is a chronic neurodevelopmental disorder with childhood onset characterized by multiple motor tics and at least one vocal tic, with symptoms persisting for over one year. Its exact etiology remains unclear. Identifying novel therapeutic targets for TS is cr...
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BMC
2025-06-01
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| Series: | Italian Journal of Pediatrics |
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| Online Access: | https://doi.org/10.1186/s13052-025-02048-x |
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| author | Shilin Zhou Lixin Li |
| author_facet | Shilin Zhou Lixin Li |
| author_sort | Shilin Zhou |
| collection | DOAJ |
| description | Abstract Background Tourette syndrome (TS) is a chronic neurodevelopmental disorder with childhood onset characterized by multiple motor tics and at least one vocal tic, with symptoms persisting for over one year. Its exact etiology remains unclear. Identifying novel therapeutic targets for TS is critically important. Methods We utilized cis-expression quantitative trait loci (cis-eQTLs) of druggable genes obtained from the eQTLGen Consortium and genome-wide association study (GWAS) data for TS from the Psychiatric Genomics Consortium as the outcome to simulate the effects of pharmacological interventions on TS via Mendelian randomization (MR). Colocalization analyses were then conducted to validate the findings. To further corroborate these results, we investigated the role of DNA methylation in mediating the relationship between druggable gene expression and TS. Results The expression of seven druggable genes was significantly associated with TS susceptibility (FDR < 0.05). TS susceptibility and three key genes (RET, CAPNS1, and LAMA5) were likely to share a causal variant. Further DNA methylation analysis identified seven critical methylation sites (cg02605258, cg02907768, cg06026331, cg09831553, cg12382846, cg19674797, and cg20752878), which indirectly influence TS development by regulating LAMA5 gene expression. Conclusion LAMA5 is the most promising potential drug target for mitigating TS risk. Our study not only reveals potential therapeutic targets but also provides directions for future TS drug development. |
| format | Article |
| id | doaj-art-db44dbd3f6cb493a808692c093ba8925 |
| institution | DOAJ |
| issn | 1824-7288 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | BMC |
| record_format | Article |
| series | Italian Journal of Pediatrics |
| spelling | doaj-art-db44dbd3f6cb493a808692c093ba89252025-08-20T02:39:44ZengBMCItalian Journal of Pediatrics1824-72882025-06-015111710.1186/s13052-025-02048-xIdentifying potential drug targets for tourette syndrome: a Mendelian randomization study based on druggable genesShilin Zhou0Lixin Li1College of Traditional Chinese Medicine, Changchun University of Chinese MedicineThe First Clinical Hospital of Jilin Academy of Traditional Chinese MedicineAbstract Background Tourette syndrome (TS) is a chronic neurodevelopmental disorder with childhood onset characterized by multiple motor tics and at least one vocal tic, with symptoms persisting for over one year. Its exact etiology remains unclear. Identifying novel therapeutic targets for TS is critically important. Methods We utilized cis-expression quantitative trait loci (cis-eQTLs) of druggable genes obtained from the eQTLGen Consortium and genome-wide association study (GWAS) data for TS from the Psychiatric Genomics Consortium as the outcome to simulate the effects of pharmacological interventions on TS via Mendelian randomization (MR). Colocalization analyses were then conducted to validate the findings. To further corroborate these results, we investigated the role of DNA methylation in mediating the relationship between druggable gene expression and TS. Results The expression of seven druggable genes was significantly associated with TS susceptibility (FDR < 0.05). TS susceptibility and three key genes (RET, CAPNS1, and LAMA5) were likely to share a causal variant. Further DNA methylation analysis identified seven critical methylation sites (cg02605258, cg02907768, cg06026331, cg09831553, cg12382846, cg19674797, and cg20752878), which indirectly influence TS development by regulating LAMA5 gene expression. Conclusion LAMA5 is the most promising potential drug target for mitigating TS risk. Our study not only reveals potential therapeutic targets but also provides directions for future TS drug development.https://doi.org/10.1186/s13052-025-02048-xTourette syndromeMendelian randomizationDruggable genesDNA methylationLAMA5 |
| spellingShingle | Shilin Zhou Lixin Li Identifying potential drug targets for tourette syndrome: a Mendelian randomization study based on druggable genes Italian Journal of Pediatrics Tourette syndrome Mendelian randomization Druggable genes DNA methylation LAMA5 |
| title | Identifying potential drug targets for tourette syndrome: a Mendelian randomization study based on druggable genes |
| title_full | Identifying potential drug targets for tourette syndrome: a Mendelian randomization study based on druggable genes |
| title_fullStr | Identifying potential drug targets for tourette syndrome: a Mendelian randomization study based on druggable genes |
| title_full_unstemmed | Identifying potential drug targets for tourette syndrome: a Mendelian randomization study based on druggable genes |
| title_short | Identifying potential drug targets for tourette syndrome: a Mendelian randomization study based on druggable genes |
| title_sort | identifying potential drug targets for tourette syndrome a mendelian randomization study based on druggable genes |
| topic | Tourette syndrome Mendelian randomization Druggable genes DNA methylation LAMA5 |
| url | https://doi.org/10.1186/s13052-025-02048-x |
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