Shared molecular and immune signatures of tic disorders and allergic diseases: a cross-disease transcriptomic analysis

Background Tic disorders (TD) are epidemiologically associated with allergic diseases, but the peripheral molecular features potentially shared by these conditions remain unclear. This study aimed to identify overlapping peripheral blood transcriptomic features across independent TD and allergic disease cohorts and to explore their associations with peripheral immune signatures. Methods Two independent Gene Expression Omnibus whole-blood transcriptomic datasets, GSE310998 (28 individuals with TD and 20 controls) and GSE141661 (248 individuals with allergic diseases and 209 controls), were analyzed using differential expression analysis and weighted gene co-expression network analysis for exploratory cross-disease candidate-gene prioritization. Reactome GSEA, ssGSEA, and CIBERSORT were used to characterize associated pathway and immune features. Male BALB/c mice were assigned to control, OVA-sensitized, IDPN-treated, or combined-treatment groups (n = 8 per group). Stereotypy, OVA-specific IgE, whole-blood Gpx7 mRNA, and the percentage of CD63-positive neutrophils were assessed. Results Exploratory integrative analysis prioritized GPX7 as a candidate gene for further investigation. The GPX7-low groups showed more pronounced neutrophil-related immune features in both datasets. The combined-treatment group exhibited higher stereotypy scores than the IDPN group, alongside lower whole-blood Gpx7 mRNA and a higher percentage of CD63-positive neutrophils than either single-treatment group. Conclusion These findings identify overlapping peripheral transcriptomic and neutrophil-related immune features across independent TD and allergic disease cohorts. Although the functional relationship between GPX7 expression and neutrophil-related alterations remains to be established, these findings provide clues to potential biological links between the two conditions.