A Weighted Gene Co-expression Network Analysis Reveals lncRNA Abnormalities in the Peripheral Blood Associated With Ultra-High-Risk for Psychosis

Objective: The primary study aim was to identify long non-coding RNA (lncRNA) abnormalities associated with ultra-high-risk (UHR) for psychosis based on a weighted gene co-expression network analysis. Methods: UHR patients were screened by the structured interview for prodromal syndromes (SIPS). We performed a WGCNA analysis on lncRNA and mRNA microarray profiles generated from the peripheral blood samples in 14 treatment-seeking patients with UHR who never received psychiatric medication and 18 demographically matched typically developing controls. Gene Ontology (GO) analysis and canonical correlation analysis were then applied to reveal functions and correlation between lncRNAs and mRNAs. Results: The lncRNAs were organized into co-expressed modules by WGCNA, two modules of which were strongly associated with UHR. The mRNA networks were constructed and two disease-associated mRNA modules were identified. A functional enrichment analysis showed that mRNAs were highly enriched for immune regulation and inflammation. Moreover, a significant correlation between lncRNAs and mRNAs were verified by a canonical correlation analysis. Conclusion: We identified novel lncRNA modules related to UHR. These results contribute to our understanding of the molecular basis of UHR from the perspective of systems biology and provide a theoretical basis for early intervention in the assumed development of schizophrenia.