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Increased co-expression of genes harboring the damaging de novo mutations in Chinese schizophrenic patients during prenatal development
Schizophrenia is a heritable, heterogeneous common psychiatric disorder. In this study, we evaluated the hypothesis that de novo variants (DNVs) contribute to the pathogenesis of schizophrenia. We performed exome sequencing in Chinese patients (N = 45) with schizophrenia and their unaffected parents...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2015
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4678883/ https://www.ncbi.nlm.nih.gov/pubmed/26666178 http://dx.doi.org/10.1038/srep18209 |
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author | Wang, Qiang Li, Miaoxin Yang, Zhenxing Hu, Xun Wu, Hei-Man Ni, Peiyan Ren, Hongyan Deng, Wei Li, Mingli Ma, Xiaohong Guo, Wanjun Zhao, Liansheng Wang, Yingcheng Xiang, Bo Lei, Wei Sham, Pak C Li, Tao |
author_facet | Wang, Qiang Li, Miaoxin Yang, Zhenxing Hu, Xun Wu, Hei-Man Ni, Peiyan Ren, Hongyan Deng, Wei Li, Mingli Ma, Xiaohong Guo, Wanjun Zhao, Liansheng Wang, Yingcheng Xiang, Bo Lei, Wei Sham, Pak C Li, Tao |
author_sort | Wang, Qiang |
collection | PubMed |
description | Schizophrenia is a heritable, heterogeneous common psychiatric disorder. In this study, we evaluated the hypothesis that de novo variants (DNVs) contribute to the pathogenesis of schizophrenia. We performed exome sequencing in Chinese patients (N = 45) with schizophrenia and their unaffected parents (N = 90). Forty genes were found to contain DNVs. These genes had enriched transcriptional co-expression profile in prenatal frontal cortex (Bonferroni corrected p < 9.1 × 10(−3)), and in prenatal temporal and parietal regions (Bonferroni corrected p < 0.03). Also, four prenatal anatomical subregions (VCF, MFC, OFC and ITC) have shown significant enrichment of connectedness in co-expression networks. Moreover, four genes (LRP1, MACF1, DICER1 and ABCA2) harboring the damaging de novo mutations are strongly prioritized as susceptibility genes by multiple evidences. Our findings in Chinese schizophrenic patients indicate the pathogenic role of DNVs, supporting the hypothesis that schizophrenia is a neurodevelopmental disease. |
format | Online Article Text |
id | pubmed-4678883 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-46788832015-12-18 Increased co-expression of genes harboring the damaging de novo mutations in Chinese schizophrenic patients during prenatal development Wang, Qiang Li, Miaoxin Yang, Zhenxing Hu, Xun Wu, Hei-Man Ni, Peiyan Ren, Hongyan Deng, Wei Li, Mingli Ma, Xiaohong Guo, Wanjun Zhao, Liansheng Wang, Yingcheng Xiang, Bo Lei, Wei Sham, Pak C Li, Tao Sci Rep Article Schizophrenia is a heritable, heterogeneous common psychiatric disorder. In this study, we evaluated the hypothesis that de novo variants (DNVs) contribute to the pathogenesis of schizophrenia. We performed exome sequencing in Chinese patients (N = 45) with schizophrenia and their unaffected parents (N = 90). Forty genes were found to contain DNVs. These genes had enriched transcriptional co-expression profile in prenatal frontal cortex (Bonferroni corrected p < 9.1 × 10(−3)), and in prenatal temporal and parietal regions (Bonferroni corrected p < 0.03). Also, four prenatal anatomical subregions (VCF, MFC, OFC and ITC) have shown significant enrichment of connectedness in co-expression networks. Moreover, four genes (LRP1, MACF1, DICER1 and ABCA2) harboring the damaging de novo mutations are strongly prioritized as susceptibility genes by multiple evidences. Our findings in Chinese schizophrenic patients indicate the pathogenic role of DNVs, supporting the hypothesis that schizophrenia is a neurodevelopmental disease. Nature Publishing Group 2015-12-15 /pmc/articles/PMC4678883/ /pubmed/26666178 http://dx.doi.org/10.1038/srep18209 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
spellingShingle | Article Wang, Qiang Li, Miaoxin Yang, Zhenxing Hu, Xun Wu, Hei-Man Ni, Peiyan Ren, Hongyan Deng, Wei Li, Mingli Ma, Xiaohong Guo, Wanjun Zhao, Liansheng Wang, Yingcheng Xiang, Bo Lei, Wei Sham, Pak C Li, Tao Increased co-expression of genes harboring the damaging de novo mutations in Chinese schizophrenic patients during prenatal development |
title | Increased co-expression of genes harboring the damaging de novo mutations in Chinese schizophrenic patients during prenatal development |
title_full | Increased co-expression of genes harboring the damaging de novo mutations in Chinese schizophrenic patients during prenatal development |
title_fullStr | Increased co-expression of genes harboring the damaging de novo mutations in Chinese schizophrenic patients during prenatal development |
title_full_unstemmed | Increased co-expression of genes harboring the damaging de novo mutations in Chinese schizophrenic patients during prenatal development |
title_short | Increased co-expression of genes harboring the damaging de novo mutations in Chinese schizophrenic patients during prenatal development |
title_sort | increased co-expression of genes harboring the damaging de novo mutations in chinese schizophrenic patients during prenatal development |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4678883/ https://www.ncbi.nlm.nih.gov/pubmed/26666178 http://dx.doi.org/10.1038/srep18209 |
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