Integrated multi‐layer transcriptomics reveals a gamma‐aminobutyric acid‐centred molecular state in Tourette syndrome
- 1Department of PediatricsAnhui Medical University Clinic Medical CollegeHefei China
- 2Department of Paediatrics First Affiliated Hospital of Anhui Medical University Hefei China
- 3Department of PediatricsAnhui Province Maternity and Child Health HospitalHefei China
Abstract
Aims Gamma‐aminobutyric acid (GABA)ergic dysfunction is central to Tourette syndrome (TS), yet evidence linking peripheral signals, upstream regulation, pharmacologic response and striatal cellular context remains fragmented. We investigated whether a GABA‐defined peripheral molecular state in TS could be linked to candidate regulatory signals, pharmacologic response, striatal cell‐type localisation, and local communication networks. Methods We integrated peripheral blood mRNA (GSE30470), serum miRNA profiles (GSE146509), chronic diazepam brain transcriptomes (GSE76700) and striatal single‐cell RNA‐seq (GSE116470). TS samples were stratified by a GABA_index derived from GABA‐related gene expression. Analyses included differential expression, miRNA target enrichment, disease‐drug reversal, cell‐type localisation, and ligand‐receptor communication. Results GABA_index stratification separated TS into GABA_Low and GABA_High states, revealing 1290 differentially expressed genes. The only high‐confidence serum miRNA was hsa‐miR‐483‐3p; enrichment of its validated targets in neurotrophin, Ras, Rap1, axon guidance and cAMP pathways indicates upstream cortico‐striato‐thalamo‐cortical (CSTC) regulation. Chronic diazepam reversed the TS transcriptional signature in cortex, negatively enriching TS_Up and positively enriching TS_Down genes. Single‐cell analysis localised GABA/CSTC programs to medium spiny neurons and interneurons; communication analysis revealed an extracellular matrix/adhesion‐centred striatal microenvironment with fibroblast and vascular leptomeningeal cell contributions. Conclusion TS is associated with a peripheral GABA‐centric molecular state linked to upstream miRNA regulation and striatal neuronal microenvironments.
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BibTeX
@article{zhao2026integrated,
title = {{Integrated multi‐layer transcriptomics reveals a gamma‐aminobutyric acid‐centred molecular state in Tourette syndrome}},
author = {Qingsong Zhao and Fathallah Yasmine and Yanan Peng and Le Liu and Juan Wang and Qian Wang and Jing Tan and Ran Hua and De Wu},
journal = {Clinical and Translational Discovery},
year = {2026},
month = oct,
doi = {10.1002/ctd2.70219},
url = {https://doi.org/10.1002/ctd2.70219},
note = {CC BY},
}
RIS
TY - JOUR
TI - Integrated multi‐layer transcriptomics reveals a gamma‐aminobutyric acid‐centred molecular state in Tourette syndrome
AU - Qingsong Zhao
AU - Fathallah Yasmine
AU - Yanan Peng
AU - Le Liu
AU - Juan Wang
AU - Qian Wang
AU - Jing Tan
AU - Ran Hua
AU - De Wu
PY - 2026
DA - 2026/10/26
JO - Clinical and Translational Discovery
DO - 10.1002/ctd2.70219
UR - https://doi.org/10.1002/ctd2.70219
AB - Aims Gamma‐aminobutyric acid (GABA)ergic dysfunction is central to Tourette syndrome (TS), yet evidence linking peripheral signals, upstream regulation, pharmacologic response and striatal cellular context remains fragmented. We investigated whether a GABA‐defined peripheral molecular state in TS could be linked to candidate regulatory signals, pharmacologic response, striatal cell‐type localisation, and local communication networks. Methods We integrated peripheral blood mRNA (GSE30470), serum miRNA profiles (GSE146509), chronic diazepam brain transcriptomes (GSE76700) and striatal single‐cell RNA‐seq (GSE116470). TS samples were stratified by a GABA_index derived from GABA‐related gene expression. Analyses included differential expression, miRNA target enrichment, disease‐drug reversal, cell‐type localisation, and ligand‐receptor communication. Results GABA_index stratification separated TS into GABA_Low and GABA_High states, revealing 1290 differentially expressed genes. The only high‐confidence serum miRNA was hsa‐miR‐483‐3p; enrichment of its validated targets in neurotrophin, Ras, Rap1, axon guidance and cAMP pathways indicates upstream cortico‐striato‐thalamo‐cortical (CSTC) regulation. Chronic diazepam reversed the TS transcriptional signature in cortex, negatively enriching TS_Up and positively enriching TS_Down genes. Single‐cell analysis localised GABA/CSTC programs to medium spiny neurons and interneurons; communication analysis revealed an extracellular matrix/adhesion‐centred striatal microenvironment with fibroblast and vascular leptomeningeal cell contributions. Conclusion TS is associated with a peripheral GABA‐centric molecular state linked to upstream miRNA regulation and striatal neuronal microenvironments.
SN - 2768-0622
ER -