CNV Deletions May Affect Schizophrenia Risks Through Lncrna Genes That Regulate Protein-Coding Genes
2017
Abstract Schizophrenia is a complex psychiatric disorder with strong genetic background. Studies demonstrated that rare Copy Number Variations (CNVs) contribute to the risk of schizophrenia. More attention has been put to protein-coding genes residing in those CNVs. However, the exact mechanisms still remain unclear. In this study, we explored the potential roles of long non-coding RNAs (lncRNAs) inside CNV deletions (CNV-lncRNAs) in the risk of schizophrenia. We retrieved lncRNAs mapped to the CNV deletion regions known to increase risks of developing schizophrenia. Seven such regions were repeatedly reported by large case-control studies, including 1q21.1, 3q29, 15q11.2, 15q13.3, 17p12, 17q12, and 22q11.2. We carried out weighted gene co-expression network analysis (WGCNA) using RNA-seq data from Genotype-Tissue Expression (GTEx) and BrainSpan projects to look for co-expression modules that harbor CNV-lncRNAs. We identified one male reproduction-related module in male individuals and one neuronal functions-related module both in male and female individuals. In addition, the neuronal functions module comprised of protein-coding genes that were involved in several ion channel activities including calcium and potassium channel activities, which were known to be related to schizophrenia. Pathway analysis of these two modules further suggested that CNV-lncRNAs were involved in the olfactory transduction, neuroactive ligand-receptor and calcium signaling pathways. The CNV-lncRNA co-expression patterns were preserved through the different development and aging time points, and across different tissue types of human body. Our results suggested that lncRNAs inside those rare CNVs might play significant temporal and spatial roles in regulating other protein-coding genes and subsequently contribute to schizophrenia risk.
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