Increased co-expression of genes harboring the damaging de novo mutations in Chinese schizophrenic patients during prenatal development

Abstract

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.

DOI: 10.1038/srep18209

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@inproceedings{Wang2015IncreasedCO, title={Increased co-expression of genes harboring the damaging de novo mutations in Chinese schizophrenic patients during prenatal development}, author={Qiang Wang and Miaoxin Li and Zhenxing Yang and Xun Hu and Hei-Man Wu and Peiyan Ni and Hongyan Ren and Wei Deng and Mingli Li and Xiaohong Ma and Wanjun Guo and Liansheng Zhao and Yingcheng Wang and Bo Xiang and Wei Lei and Pak C. Sham and Tao Li}, booktitle={Scientific reports}, year={2015} }