ArticleBrain and behavior2025
ZDHHC5 Mediates Immune Dysregulation Driving Generalized Anxiety Disorder Risk.
Article in Brain and behavior, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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Who cites it
2 citing papers in PubMed.
- ZDHHC5 may regulate the function of NKT cells and the immune response in Meniere's disease.Mammalian genome : official journal of the International Mammalian Genome Society · 2026Article
- ZDHHC5 Mediates Immune Dysregulation Driving Generalized Anxiety Disorder Risk.Brain and behavior · 2025Article
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTo investigate genes associated with palmitoylation modification implicated in generalized anxiety disorder (GAD), and to elucidate the mechanistic roles of these genes via immune cell-mediated pathways.
methodsUtilizing large-scale genetic datasets, genes categorized as palmitoylation-expression quantitative trait loci (eQTL) were identified by intersecting palmitoylation-related genes (as compiled from the most recent reviews) with genome-wide eQTL datasets. A two-sample Mendelian randomization (MR) methodology was applied to investigate the causal relationship between palmitoylation-eQTL genes and GAD, with further verification conducted through summary-data-based Mendelian randomization (SMR) to establish the final target genes. Subsequently, the underlying mechanisms of these genes were examined through immune cell-mediated processes.
resultsTwenty-two palmitoylation-eQTL gene loci were identified, among which five demonstrated a notable link to GAD: PPT2 (odds ratio [OR] = 0.844, p = 0.007), ZDHHC5 (OR = 1.101, p = 0.017), ZDHHC13 (OR = 1.175, p < 0.001), ZDHHC20 (OR = 0.874, p = 0.003), and ZDHHC24 (OR = 0.806, p < 0.001). ZDHHC5 and ZDHHC13 were validated as final target genes through SMR analysis. Mediation MR analysis revealed that SSC-A on CD4+ T cells (mediation proportion: 36.4%) served as a mediating factor for ZDHHC5.
conclusionThe findings indicate that ZDHHC5 contributes to the pathogenesis of GAD by modulating SSC-A on CD4+ T cells, thereby offering novel targets for the investigation of GAD pathophysiology.
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