{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:05:08Z","timestamp":1753891508456,"version":"3.41.2"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T00:00:00Z","timestamp":1655337600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Aging Neurosci."],"abstract":"<jats:p>Childhood-onset schizophrenia (COS) is an unusual severe neurodevelopmental disorder of unknown etiology. In this study, we aimed to survey the missense variants in new cases of COS and also identify possible pathology biomarkers for COS. We found one list of mutated genes such as TTN, MUC12, and MUC2, which are the candidates to be involved in the etiology of COS. Next, we used WGSNA to predict COS disease-related genes and identified differential DNA methylation among COS disease groups, COS dangerous groups, and normal groups and found eight methylation sites that can be used as the diagnostic biomarkers. A total of six key genes are obtained through the intersection analysis between weighted correlation network analysis (WGCNA) mode, methylation-related genes, and differentially expressed genes (DGenes). These genes may play important roles in the progression of COS and serve as the potential biomarkers for future diagnosis. Our results might help to design the molecule or gene-targeted drugs for COS.<\/jats:p>","DOI":"10.3389\/fnagi.2022.829217","type":"journal-article","created":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T06:01:26Z","timestamp":1655359286000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Exploration of Mutated Genes and Prediction of Potential Biomarkers for Childhood-Onset Schizophrenia Using an Integrated Bioinformatic Analysis"],"prefix":"10.3389","volume":"14","author":[{"given":"Fan","family":"He","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-ming","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan-jie","family":"Qi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huan-huan","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Guan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-hang","family":"Cheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1007\/s11920-009-0024-y","article-title":"The genetics of childhood-onset schizophrenia: when madness strikes the prepubescent.","volume":"11","author":"Addington","year":"2009","journal-title":"Curr. Psychiatry Rep."},{"key":"B2","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1038\/sj.mp.4001599","article-title":"GAD1 (2q31.1), which encodes glutamic acid decarboxylase (GAD67), is associated with childhood-onset schizophrenia and cortical gray matter volume loss.","volume":"10","author":"Addington","year":"2005","journal-title":"Mol. Psychiatry"},{"key":"B3","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1038\/mp.2013.59","article-title":"High rate of disease-related copy number variations in childhood onset schizophrenia.","volume":"19","author":"Ahn","year":"2014","journal-title":"Mol. Psychiatry"},{"key":"B4","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1016\/j.ajhg.2010.07.019","article-title":"Direct measure of the de novo mutation rate in autism and schizophrenia cohorts.","volume":"87","author":"Awadalla","year":"2010","journal-title":"Am. J. Hum. Genet."},{"key":"B5","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1097\/00054725-199902000-00004","article-title":"Abnormalities in mucin gene expression in Crohn\u2019s disease.","volume":"5","author":"Buisine","year":"1999","journal-title":"Inflamm. Bowel Dis."},{"key":"B6","doi-asserted-by":"publisher","first-page":"19096","DOI":"10.1073\/pnas.0910672106","article-title":"Genetic diagnosis by whole exome capture and massively parallel DNA sequencing.","volume":"106","author":"Choi","year":"2009","journal-title":"Proc. Natl. Acad. Sci. U.S.A."},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2164-15-300","article-title":"Visual gene-network analysis reveals the cancer gene co-expression in human endometrial cancer.","volume":"15","author":"Chou","year":"2014","journal-title":"BMC Genomics"},{"key":"B8","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1038\/ng.806","article-title":"A framework for variation discovery and genotyping using next-generation DNA sequencing data.","volume":"43","author":"DePristo","year":"2011","journal-title":"Nat. Genet."},{"key":"B9","doi-asserted-by":"publisher","first-page":"344","DOI":"10.1038\/nature13394","article-title":"Genome sequencing identifies major causes of severe intellectual disability.","volume":"511","author":"Gilissen","year":"2014","journal-title":"Nature"},{"key":"B10","doi-asserted-by":"publisher","first-page":"860","DOI":"10.1038\/ng.886","article-title":"Increased exonic de novo mutation rate in individuals with schizophrenia.","volume":"43","author":"Girard","year":"2011","journal-title":"Nat. Genet."},{"key":"B11","doi-asserted-by":"publisher","first-page":"831","DOI":"10.1007\/s10803-005-0028-3","article-title":"Dysbindin (DTNBP1, 6p22.3) is associated with childhood-onset psychosis and endophenotypes measured by the Premorbid Adjustment Scale (PAS).","volume":"35","author":"Gornick","year":"2005","journal-title":"J. Autism Dev. Disord."},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008232","article-title":"Exome sequencing of a multigenerational human pedigree.","volume":"4","author":"Hedges","year":"2009","journal-title":"PLoS One"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.compbiomed.2019.103380","article-title":"Comparison of methods for differential co-expression analysis for disease biomarker prediction.","volume":"113","author":"Kakati","year":"2019","journal-title":"Comput. Biol. Med."},{"key":"B14","doi-asserted-by":"publisher","first-page":"554","DOI":"10.1007\/s10517-006-0022-6","article-title":"Induction of differentiation in leukemic cell strains with myelopeptide-4.","volume":"140","author":"Kirilina","year":"2005","journal-title":"Bull. Exp. Biol. Med."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-9-559","article-title":"WGCNA: an R package for weighted correlation network analysis.","volume":"9","author":"Langfelder","year":"2008","journal-title":"BMC Bioinformatics"},{"key":"B16","doi-asserted-by":"crossref","DOI":"10.1038\/s41398-020-0708-y","article-title":"Novel genetic susceptibility loci identified by family based whole exome sequencing in Han Chinese schizophrenia patients.","volume":"10","author":"Li","year":"2020","journal-title":"Transl. Psychiatry"},{"key":"B17","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1016\/j.biocel.2010.03.001","article-title":"Human intestinal MUC17 mucin augments intestinal cell restitution and enhances healing of experimental colitis.","volume":"42","author":"Luu","year":"2010","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1101\/gr.107524.110","article-title":"The Genome Analysis Toolkit: a MapReduce framework for analyzing next-generation DNA sequencing data.","volume":"20","author":"McKenna","year":"2010","journal-title":"Genome Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1055","DOI":"10.1007\/s00109-006-0100-2","article-title":"Aberrant intestinal expression and allelic variants of mucin genes associated with inflammatory bowel disease.","volume":"84","author":"Moehle","year":"2006","journal-title":"J. Mol. Med. (Berl)"},{"key":"B20","doi-asserted-by":"publisher","first-page":"839","DOI":"10.1038\/s41380-018-0129-y","article-title":"Somatic mutations in the human brain: implications for psychiatric research.","volume":"24","author":"Nishioka","year":"2019","journal-title":"Mol. Psychiatry"},{"key":"B21","doi-asserted-by":"publisher","first-page":"585","DOI":"10.1038\/ng.835","article-title":"Exome sequencing in sporadic autism spectrum disorders identifies severe de novo mutations.","volume":"43","author":"O\u2019Roak","year":"2011","journal-title":"Nat. Genet."},{"key":"B22","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1046\/j.1440-1614.2003.01203.x","article-title":"Prevalence and course of schizophrenia in a Chinese rural area.","volume":"37","author":"Ran","year":"2003","journal-title":"Aust. N. Z. J. Psychiatry"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1186\/gm13","article-title":"The human gene mutation database: 2008 update.","volume":"1","author":"Stenson","year":"2009","journal-title":"Genome Med."},{"key":"B24","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1007\/s12031-019-01382-0","article-title":"Age matters: an atypical association between polymorphism of mthfr and clinical phenotypes in children with schizophrenia.","volume":"69","author":"Wan","year":"2019","journal-title":"J. Mol. Neurosci."},{"key":"B25","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1001\/archpsyc.1987.01800190080012","article-title":"Implications of normal brain development for the pathogenesis of schizophrenia.","volume":"44","author":"Weinberger","year":"1987","journal-title":"Arch. Gen. Psychiatry"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1491","DOI":"10.4155\/fmc.13.141","article-title":"Therapeutic potential of isoform selective HDAC inhibitors for the treatment of schizophrenia.","volume":"5","author":"We\u00efwer","year":"2013","journal-title":"Future Med. Chem."},{"key":"B27","doi-asserted-by":"crossref","DOI":"10.3389\/fnmol.2016.00114","article-title":"Aberrant expression of histone deacetylases 4 in cognitive disorders: molecular mechanisms and a potential target.","volume":"9","author":"Wu","year":"2016","journal-title":"Front. Mol. Neurosci."},{"key":"B28","doi-asserted-by":"crossref","first-page":"864","DOI":"10.1038\/ng.902","article-title":"Exome sequencing supports a de novo mutational paradigm for schizophrenia.","volume":"43","author":"Xu","year":"2011","journal-title":"Nat. Genet."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.comppsych.2020.152176","article-title":"Sex differences in circulating neuregulin1-\u03b21 and \u03b2-secretase 1 expression in childhood-onset schizophrenia.","volume":"100","author":"Zhang","year":"2020","journal-title":"Compr. Psychiatry"}],"container-title":["Frontiers in Aging Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2022.829217\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,16]],"date-time":"2022-06-16T06:01:30Z","timestamp":1655359290000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnagi.2022.829217\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,16]]},"references-count":29,"alternative-id":["10.3389\/fnagi.2022.829217"],"URL":"https:\/\/doi.org\/10.3389\/fnagi.2022.829217","relation":{},"ISSN":["1663-4365"],"issn-type":[{"type":"electronic","value":"1663-4365"}],"subject":[],"published":{"date-parts":[[2022,6,16]]},"article-number":"829217"}}