Evidence mapPaperPMID 40490792Full record

ArticleItalian journal of pediatrics2025

Identifying potential drug targets for tourette syndrome: a Mendelian randomization study based on druggable genes.

Shilin Zhou, Lixin Li

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Article in Italian journal of pediatrics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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5 · Who and what money

Authors and funding

2 authors.

Shilin ZhouCollege of Traditional Chinese Medicine, Changchun University of Chinese Medicine, Changchun, China.
Lixin LiThe First Clinical Hospital of Jilin Academy of Traditional Chinese Medicine, Changchun, China. 951833053@qq.com.ORCID http://orcid.org/0009-0004-3657-912X

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundTourette 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.

methodsWe 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.

resultsThe 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.

conclusionLAMA5 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.

Indexed as

Mendelian Randomization AnalysisTourette SyndromeDNA MethylationGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansLamininQuantitative Trait LociLamininDNA methylationDruggable genesLAMA5Mendelian randomizationTourette syndrome

Identifiers

PMID40490792
PMCPMC12150520

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