Abstract
Schizophrenia (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 as APC, CACNB2, and PRKN, were found, and an enrichment of binding sites for brain-expressed transcription factors, such as FOXO1, MYB, and ZIC3, was also observed. Moreover, a protein-protein interaction network showed a central role for DISC1 and ZNF688 genes, and experimentally validated targets of MIR-137, such as and KCNB2, NRXN1, and SYN2, 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.
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YG-G was previously supported by a PhD fellowship from Centro de Estudios Interdisciplinarios Básicos y Aplicados CEIBA (Rodolfo Llinás Program). DAF was previously supported by research grants from Colciencias.
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All authors contributed to the study conception and design. Data collection and analysis were performed by DAF and YG-G. The first draft of the manuscript was written by DAF and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Forero, D.A., González-Giraldo, Y. Integrative In Silico Analysis of Genome-Wide DNA Methylation Profiles in Schizophrenia. J Mol Neurosci 70, 1887–1893 (2020). https://doi.org/10.1007/s12031-020-01585-w
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DOI: https://doi.org/10.1007/s12031-020-01585-w