Converging evidence implicates the abnormal microRNA system in schizophrenia

Fuquan Zhang, Yong Xu, Yin Yao Shugart, Weihua Yue, Guoyang Qi, Guozhen Yuan, Zaohuo Cheng, Jianjun Yao, Jidong Wang, Guoqiang Wang, Hongbao Cao, Wei Guo, Zhenhe Zhou, Zhiqiang Wang, Lin Tian, Chunhui Jin, Jianmin Yuan, Chenxing Liu, Dai Zhang

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)728-735
Number of pages8
JournalSchizophrenia Bulletin
Volume41
Issue number3
DOIs
StatePublished - 2015

Keywords

  • Early-onset
  • MicroRNA
  • mRNA
  • Rare variants
  • Schizophrenia

ASJC Scopus subject areas

  • Psychiatry and Mental health

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