title: Converging evidence implicates the abnormal microRNA system in schizophrenia.
abstract: BACKGROUND
  Previous findings are inconsistent; yet, converging evidence suggests an association between schizophrenia (SZ) and the impairment of posttranscriptional regulation of brain development through microRNA (miRNA) systems.
  
  
  METHODS
  This study aims to (1) compare the overall frequency of 121 rare variants (RVs) in 59 genes associated with the miRNA system in genome-wide association studies (GWAS)-derived data including 768 SZ cases and 1348 healthy controls and validated in an independent GWAS data including 1802 SZ cases and 1447 controls; (2) profile genome-wide miRNA expression in blood collected from 15 early-onset SZ (EOS) cases and 15 healthy controls; and (3) construct a miRNA-messenger RNA (mRNA) regulatory network using our previous genome-wide mRNA expression data generated from a separate sample of 18 EOS cases and 12 healthy controls.
  
  
  RESULTS
  Our findings indicate that: (1) In genes associated with the control of miRNAs, there are approximately 50% more RVs in SZ cases than in controls (P ≤ 2.62E-10); (2) The observed lower miRNA activity in EOS patients compared with the healthy controls suggests that miRNAs are abnormally downregulated; (3) There exists a predicted regulatory network among some downregulated miRNAs and some upregulated mRNAs.
  
  
  CONCLUSIONS
  Collectively, results from all 3 lines of evidence, suggest that the genetically based dysregulation of miRNA systems undermines miRNAs' inhibitory effects, resulting in the abnormal upregulation of genome transcription in the development of SZ.
authors.forename: Fuquan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Psychiatry, First Hospital of Shanxi Medical University, Taiyuan, China;
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Division of Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD; Department of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, MD;
authors.forename: Yin Yao
authors.initials: YY
authors.lastname: Shugart
authors.affiliation: Department of Psychiatry, The Sixth Afﬁliated Hospital and Institute for Mental Health of Peking University/Key Laboratory of Mental Health, Ministry of Health, Beijing, China;
authors.forename: Weihua
authors.initials: W
authors.lastname: Yue
authors.affiliation: Department of Clinical Psychology, Wuxi Mental Health Center of Nanjing Medical University, Wuxi, China;
authors.forename: Guoyang
authors.initials: G
authors.lastname: Qi
authors.affiliation: Department of Clinical Psychology, Wuxi Mental Health Center of Nanjing Medical University, Wuxi, China;
authors.forename: Guozhen
authors.initials: G
authors.lastname: Yuan
authors.affiliation: Department of Clinical Psychology, Wuxi Mental Health Center of Nanjing Medical University, Wuxi, China;
authors.forename: Zaohuo
authors.initials: Z
authors.lastname: Cheng
authors.affiliation: Department of Clinical Psychology, Wuxi Mental Health Center of Nanjing Medical University, Wuxi, China;
authors.forename: Jianjun
authors.initials: J
authors.lastname: Yao
authors.affiliation: Department of Clinical Psychology, Wuxi Mental Health Center of Nanjing Medical University, Wuxi, China;
authors.forename: Jidong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Clinical Psychology, Wuxi Mental Health Center of Nanjing Medical University, Wuxi, China;
authors.forename: Guoqiang
authors.initials: G
authors.lastname: Wang
authors.affiliation: Division of Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD;
authors.forename: Hongbao
authors.initials: H
authors.lastname: Cao
authors.affiliation: Division of Intramural Research Program, National Institute of Mental Health, National Institutes of Health, Bethesda, MD;
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.affiliation: Department of Clinical Psychology, Wuxi Mental Health Center of Nanjing Medical University, Wuxi, China;
authors.forename: Zhenhe
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Clinical Psychology, Wuxi Mental Health Center of Nanjing Medical University, Wuxi, China;
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Clinical Psychology, Wuxi Mental Health Center of Nanjing Medical University, Wuxi, China;
authors.forename: Lin
authors.initials: L
authors.lastname: Tian
authors.affiliation: Department of Clinical Psychology, Wuxi Mental Health Center of Nanjing Medical University, Wuxi, China;
authors.forename: Chunhui
authors.initials: C
authors.lastname: Jin
authors.affiliation: Department of Clinical Psychology, Wuxi Mental Health Center of Nanjing Medical University, Wuxi, China;
authors.forename: Jianmin
authors.initials: J
authors.lastname: Yuan
authors.affiliation: Department of Psychiatry, The Sixth Afﬁliated Hospital and Institute for Mental Health of Peking University/Key Laboratory of Mental Health, Ministry of Health, Beijing, China;
authors.forename: Chenxing
authors.initials: C
authors.lastname: Liu
authors.affiliation: Department of Psychiatry, The Sixth Afﬁliated Hospital and Institute for Mental Health of Peking University/Key Laboratory of Mental Health, Ministry of Health, Beijing, China; Peking-Tsinghua Center for Life Sciences/PKU-IDG/McGovern Institute for Brain Research, Peking University, Beijing, China daizhang@bjmu.edu.cn.
authors.forename: Dai
authors.initials: D
authors.lastname: Zhang
mesh_terms: D000293:Adolescent; D017668:Age of Onset; D002648:Child; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012559:Schizophrenia / Q000235:genetics*
chemical_list: D035683:MicroRNAs
keywords: early-onset; mRNA; microRNA; rare variants; schizophrenia