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.

精神分裂症（SZ）是一种复杂而严重的精神疾病，其全球终生患病率为0.4%，遗传力约为0.81。已经对 SZ 进行了许多表观基因组范围的关联研究 (EWAS)，但结果不一致。本研究的主要目的是对精神分裂症中可用的全基因组 DNA 甲基化谱进行综合计算机分析。在这项工作中，整合了多个证据（来自几个 EWAS 和全基因组表达和关联数据的顶级候选基因），以确定 SZ 的顶级差异甲基化 (DM) 基因。此外，还进行了功能富集和蛋白质-蛋白质相互作用分析。几个顶级差异甲基化基因，如APC、CACNB2和PRKN，发现，并且还观察到脑表达转录因子（如FOXO1、MYB和ZIC3 ）的结合位点富集。此外，蛋白质-蛋白质相互作用网络显示出DISC1和ZNF688基因的核心作用，并且在 DM 基因中鉴定了经过实验验证的 MIR-137 靶标，例如KCNB2、NRXN1和SYN2 。这是对精神分裂症中可用的全基因组 DNA 甲基化谱的第一次综合计算机分析。这项工作确定了 SZ 的新候选基因和途径，并为在未来研究中探索它们在 SZ 发病机制中的作用提供了基础。