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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
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.
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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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