Integrative In Silico Analysis of Genome-Wide DNA Methylation Profiles in Schizophrenia

AbstractSchizophrenia (SZ) is a complex and severe psychiatric disorder, which has a global lifetime prevalence of 0.4% and a heritability of around 0.81. A number of epigenome-wide association studies (EWAS) have been carried out for SZ, with discordant results. The main aim of this study was to carry out an integrative in silico analysis of available genome-wide DNA methylation profiles in schizophrenia. In this work, an integration of multiple lines of evidence (top candidate genes from several EWAS and genome-wide expression and association data) was carried out, in order to identify top differentially methylated (DM) genes for SZ. In addition, functional enrichment and protein-protein interaction analyses were carried out. Several top differentially methylated genes, such asAPC, CACNB2, andPRKN, were found, and an enrichment of binding sites for brain-expressed transcription factors, such asFOXO1, MYB, andZIC3, was also observed. Moreover, a protein-protein interaction network showed a central role forDISC1 andZNF688 genes, and experimentally validated targets of MIR-137, such as andKCNB2, NRXN1, andSYN2, were identified among DM genes. This is the first integrative in silico analysis of available genome-wide DNA methylation profiles in schizophrenia. This work identified novel candidate genes and pathways for SZ and provides the basis to explore their role in the pathogenesis of SZ in future studies.
Source: Journal of Molecular Neuroscience - Category: Neuroscience Source Type: research