Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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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PMID:Integrative In Silico Analysis of Genome-Wide DNA Methylation Profiles in Schizophrenia. 3245 40

Mutations in the family of neurexins (NRXN1, NRXN2 and NRXN3) have been repeatedly identified in patients with autism spectrum disorder (ASD) and schizophrenia (SCZ). However, it remains unclear how these DNA variants affect neurexin functions and thereby predispose to these neurodevelopmental disorders. Understanding both the wild-type and pathologic roles of these genes in the brain could help unveil biological mechanisms underlying mental disorders. In this regard, numerous studies have focused on generating relevant loss-of-function (LOF) mammalian models. Although this has increased our knowledge about their normal functions, the potential pathologic role(s) of these human variants remains elusive. Indeed, after reviewing the literature, it seems apparent that a traditional LOF-genetic approach based on complete LOF might not be sufficient to unveil the role of these human mutations. First, these genes present a very complex transcriptome and total-LOF of all isoforms may not be the cause of toxicity in patients, particularly given evidence that causative variants act through haploinsufficiency. Moreover, human DNA variants may not all lead to LOF but potentially to intricate transcriptome changes that could also include the generation of aberrant isoforms acting as a gain-of-function (GOF). Furthermore, their transcriptomic complexity most likely renders them prone to genetic compensation when one tries to manipulate them using traditional site-directed mutagenesis approaches, and this could act differently from model to model leading to heterogeneous and conflicting phenotypes. This review compiles the relevant literature on variants identified in human studies and on the mouse models currently deployed, and offers suggestions for future research.
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PMID:Neurexins in autism and schizophrenia-a review of patient mutations, mouse models and potential future directions. 3319 96


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