Lymphoblast transcriptome analysis in 22q11.2 deletion syndrome individuals with schizophrenia-spectrum disorder.
Elena MichaelovskyMiri CarmelDoron GothelfAbraham WeizmanPublished in: The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry (2024)
Objectives: 22q11.2 deletion is the most prominent risk factor for schizophrenia (SZ). The aim of the present study was to identify unique transcriptome profile for 22q11.2 deletion syndrome (DS)-related SZ spectrum disorder (SZ-SD). Methods: We performed RNA-Seq screening in lymphoblasts collected from 20 individuals with 22q11.2DS (10 men and 10 women, 4 of each sex with SZ-SD and 6 with no psychotic disorders (Np)). Results: Sex effect in RNA-Seq descriptive analysis led to separating the analyses between men and women. In women, only one differentially expressed gene (DEG), HLA-DQA2, was associated with SZ-SD. In men, 48 DEGs (adjp < 0.05) were found to be associated with SZ-SD. Ingenuity pathway analysis of top 85 DEGs (p < 4.66E-04) indicated significant enrichment for immune-inflammatory response (IIR) and neuro-inflammatory signaling pathways. Additionally, NFATC2, IFNG, IFN-alpha, STAT1 and IL-4 were identified as upstream regulators. Co-expression network analysis revealed the contribution of endoplasmic reticulum protein processing and N-Glycan biosynthesis. These findings indicate dysregulation of IIR and post-translational protein modification processes in individuals with 22q11.2DS-related SZ-SD. Conclusions: Candidate pathways and upstream regulators may serve as novel biomarkers and treatment targets for SZ. Future transcriptome studies, including larger samples and proteomic analysis, are needed to substantiate our findings.
Keyphrases
- rna seq
- single cell
- spectrum disorder
- bipolar disorder
- inflammatory response
- network analysis
- endoplasmic reticulum
- signaling pathway
- genome wide
- case report
- transcription factor
- oxidative stress
- cell proliferation
- binding protein
- cross sectional
- adipose tissue
- lipopolysaccharide induced
- protein protein
- metabolic syndrome
- dna methylation
- pi k akt
- pregnant women
- insulin resistance
- drug induced
- pregnancy outcomes
- case control