Identification of Brain Cell Type-Specific Therapeutic Targets for Glioma From Genetics.

Autor: Gui J; The 2nd Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.; Jiangxi Province Key Laboratory of Neurological Diseases, Nanchang, Jiangxi, China.; JXHC Key Laboratory of Neurological Medicine, Nanchang, Jiangxi, China.; Institute of Neuroscience, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.; HuanKui Academy, Jiangxi Medical College, Nanchang University, Nanchang, China., Chen J; The 2nd Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China., Wan K; The First Clinical Medical College, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China., Liu Y; The First Clinical Medical College, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China., Huang K; The 2nd Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.; Jiangxi Province Key Laboratory of Neurological Diseases, Nanchang, Jiangxi, China.; JXHC Key Laboratory of Neurological Medicine, Nanchang, Jiangxi, China.; Institute of Neuroscience, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.; The MOE Basic Research and Innovation Center for the Targeted Therapeutics of Solid Tumors, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China., Zhu X; The 2nd Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.; Jiangxi Province Key Laboratory of Neurological Diseases, Nanchang, Jiangxi, China.; JXHC Key Laboratory of Neurological Medicine, Nanchang, Jiangxi, China.; Institute of Neuroscience, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China.
Jazyk: angličtina
Zdroj: CNS neuroscience & therapeutics [CNS Neurosci Ther] 2024 Dec; Vol. 30 (12), pp. e70185.
DOI: 10.1111/cns.70185
Abstrakt: Background: Previous research has demonstrated correlations between the complex types and functions of brain cells and the etiology of glioma. However, the causal relationship between gene expression regulation in specific brain cell types and glioma risk, along with its therapeutic implications, remains underexplored.
Methods: Utilizing brain cell type-specific cis-expression quantitative trait loci (cis-eQTLs) and glioma genome-wide association study (GWAS) datasets in conjunction with Mendelian randomization (MR) and colocalization analyses, we conducted a systematic investigation to determine whether an association exists between the gene expression of specific brain cell types and the susceptibility to glioma, including its subtypes. Additionally, the potential pathogenicity was explored utilizing mediation and bioinformatics analyses. This exploration ultimately led to the identification of a series of brain cell-specific therapeutic targets.
Results: A total of 110 statistically significant and robust associations were identified through MR analysis, with most genes exhibiting causal effects exclusively in specific brain cell types or glioma subtypes. Bayesian colocalization analysis validated 36 associations involving 26 genes as potential brain cell-specific therapeutic targets. Mediation analysis revealed genes indirectly influencing glioma risk via telomere length. Bioinformatics analysis highlighted the involvement of these genes in glioma pathogenesis pathways and supported their enrichment in specific brain cell types.
Conclusions: This study, employing an integrated approach, demonstrated the genetic susceptibility between brain cell-specific gene expression and the risk of glioma and its subtypes. Its findings offer novel insights into glioma etiology and underscore potential therapeutic targets specific to brain cell types.
(© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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