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Sci Transl Med. 2018 Dec 19;10(472). pii: eaat6912. doi: 10.1126/scitranslmed.aat6912. Epub 2018 Dec 13.

The DGCR5 long noncoding RNA may regulate expression of several schizophrenia-related genes.

Author information

1
Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
2
Institute for Genomics and Systems Biology, University of Chicago, Chicago, IL, USA.
3
Colorado Center for Personalized Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045, USA.
4
Department of Psychiatry, SUNY Upstate Medical University, Syracuse, NY, USA.
5
Departments of Pharmacology and Biochemistry and Molecular Biology, Institute for Personalized Medicine, Penn State College of Medicine, Hershey, PA 17033, USA.
6
Department of Neuroscience and Kavli Institute for Neuroscience, Yale School of Medicine, New Haven, CT, USA.
7
Tempus Labs Inc., Chicago, IL 60654, USA.
8
Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China. chenchao@sklmg.edu.cn liuch@upstate.edu.
9
National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
10
School of Psychology, Shaanxi Normal University, Xian, Shaanxi, China.

Abstract

A number of studies indicate that rare copy number variations (CNVs) contribute to the risk of schizophrenia (SCZ). Most of these studies have focused on protein-coding genes residing in the CNVs. Here, we investigated long noncoding RNAs (lncRNAs) within 10 SCZ risk-associated CNV deletion regions (CNV-lncRNAs) and examined their potential contribution to SCZ risk. We used RNA sequencing transcriptome data derived from postmortem brain tissue from control individuals without psychiatric disease as part of the PsychENCODE BrainGVEX and Developmental Capstone projects. We carried out weighted gene coexpression network analysis to identify protein-coding genes coexpressed with CNV-lncRNAs in the human brain. We identified one neuronal function-related coexpression module shared by both datasets. This module contained a lncRNA called DGCR5 within the 22q11.2 CNV region, which was identified as a hub gene. Protein-coding genes associated with SCZ genome-wide association study signals, de novo mutations, or differential expression were also contained in this neuronal module. Using DGCR5 knockdown and overexpression experiments in human neural progenitor cells derived from human induced pluripotent stem cells, we identified a potential role for DGCR5 in regulating certain SCZ-related genes.

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