title: 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.
authors.affiliation: Mental Health Center, West China Hospital, Sichuan University, Chengdu, Sichuan, P R China.|State Key Laboratory of Biotherapy, Psychiatric laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, P R China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Brain and Cognitive Sciences, Centre for Genomic Sciences and Department of Psychiatry, University of Hong Kong, Pokfulam, S.A.R. China.
authors.forename: Miaoxin
authors.initials: M
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biotherapy, Psychiatric laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, P R China.|State Key Laboratory of Brain and Cognitive Sciences, Centre for Genomic Sciences and Department of Psychiatry, University of Hong Kong, Pokfulam, S.A.R. China.
authors.forename: Zhenxing
authors.initials: Z
authors.lastname: Yang
authors.affiliation: Biobank, West China Hospital, Sichuan University, Chengdu, Sichuan, P R China.
authors.forename: Xun
authors.initials: X
authors.lastname: Hu
authors.affiliation: State Key Laboratory of Brain and Cognitive Sciences, Centre for Genomic Sciences and Department of Psychiatry, University of Hong Kong, Pokfulam, S.A.R. China.
authors.forename: Hei-Man
authors.initials: HM
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Biotherapy, Psychiatric laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, P R China.
authors.forename: Peiyan
authors.initials: P
authors.lastname: Ni
authors.affiliation: Mental Health Center, West China Hospital, Sichuan University, Chengdu, Sichuan, P R China.
authors.forename: Hongyan
authors.initials: H
authors.lastname: Ren
authors.affiliation: Mental Health Center, West China Hospital, Sichuan University, Chengdu, Sichuan, P R China.
authors.forename: Wei
authors.initials: W
authors.lastname: Deng
authors.affiliation: Mental Health Center, West China Hospital, Sichuan University, Chengdu, Sichuan, P R China.
authors.forename: Mingli
authors.initials: M
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biotherapy, Psychiatric laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, P R China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Ma
authors.affiliation: Mental Health Center, West China Hospital, Sichuan University, Chengdu, Sichuan, P R China.
authors.forename: Wanjun
authors.initials: W
authors.lastname: Guo
authors.affiliation: State Key Laboratory of Biotherapy, Psychiatric laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, P R China.
authors.forename: Liansheng
authors.initials: L
authors.lastname: Zhao
authors.affiliation: State Key Laboratory of Biotherapy, Psychiatric laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, P R China.
authors.forename: Yingcheng
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Mental Health Center, West China Hospital, Sichuan University, Chengdu, Sichuan, P R China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xiang
authors.affiliation: Mental Health Center, West China Hospital, Sichuan University, Chengdu, Sichuan, P R China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lei
authors.affiliation: State Key Laboratory of Brain and Cognitive Sciences, Centre for Genomic Sciences and Department of Psychiatry, University of Hong Kong, Pokfulam, S.A.R. China.
authors.forename: Pak C
authors.initials: PC
authors.lastname: Sham
authors.affiliation: Mental Health Center, West China Hospital, Sichuan University, Chengdu, Sichuan, P R China.|State Key Laboratory of Biotherapy, Psychiatric laboratory, West China Hospital, Sichuan University, Chengdu, Sichuan, P R China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D044466:Asian People / Q000235:genetics*; D001921:Brain / Q000503:physiopathology; D002648:Child; D002675:Child, Preschool; D002681:China; D019295:Computational Biology / Q000379:methods; D056915:DNA Copy Number Variations; D047108:Embryonic Development / Q000235:genetics*; D059472:Exome; D005260:Female; D015870:Gene Expression; D020869:Gene Expression Profiling; D005808:Genes, Recessive; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D057895:Haploinsufficiency; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007223:Infant; D008297:Male; D009154:Mutation; D012559:Schizophrenia / Q000175:diagnosis / Q000235:genetics*; D055815:Young Adult