Search: 
Home | Contact | Sitemap | 中文 | CAS
  
  About Research Education Partnerships People Resources  
Location:Location: Home>>Papers
   
LeaderShip
CAS Members
Principal Investigator
 
Identification of the Primate-specific Gene BTN3A2 as an Additional Schizophrenia Risk Gene in the MHC Loci
author: Wu Y, Bi R, Zeng C, Ma C, Sun C, Li J, Xiao X, Li M, Zhang DF, Zheng P, Sheng N, Luo XJ, Yao YG
Abstract:

 

BACKGROUND:

Schizophrenia is a complex mental disorder resulting in poor life quality and high social and economic burden. Despite the fact that genome-wide association studies (GWASs) have successfully identified a number of risk loci for schizophrenia, identifying the causal genes at the risk loci and elucidating their roles in disease pathogenesis remain major challenges.

METHODS:

The summary data-based Mendelian randomization analysis (SMR) was used to integrate a large-scale GWAS of schizophreniawith brain expression quantitative trait loci (eQTL) data and brain methylation expression quantitative trait loci (meQTL) data, to identify novel risk gene(s) for schizophrenia. We then analyzed the mRNA expression and methylation statuses of the gene hit BTN3A2 during the early brain development. Electrophysiological analyses of CA1 pyramidal neurons were performed to evaluate the excitatory and inhibitory synaptic activity after overexpression of BTN3A2 in rat hippocampal slices. Cell surface binding assay was used to test the interaction of BTN3A2 and neurexins.

FINDINGS:

We identified BTN3A2 as a potential risk gene for schizophrenia. The mRNA expression and methylation data showed that BTN3A2 expression in human brain is highest post-natally. Further electrophysiological analyses of rat hippocampal slices showed that BTN3A2 overexpression specifically suppressed the excitatory synaptic activity onto CA1 pyramidal neurons, most likely through its interaction with the presynaptic adhesion molecule neurexins.

INTERPRETATION:

Increased expression of BTN3A2 might confer risk for schizophrenia by altering excitatory synaptic function. Our result constitutes a paradigm for distilling risk gene using an integrative analysis and functional characterization in the post-GWAS era.

Contact the author:
Page number:
Issue:
Subject:
Authors units:
PubYear: 2019
Volume:
Unit code: 152453
Publication name: EBioMedicine
The full text link: Download
Full papers: Download
Departmens of first author:
Paper source: https://www.ebiomedicine.com/article/S2352-3964(19)30307-X/fulltext
Paper type:
Participation of the author:
EMAIL:
 
  Home Mail Login Intranet login Living and Working in Kunming
Copyright© Kunming Institute of Zoology Chinese Academy of Sciences .All Rights Reserved
Address:No.32 Jiaochang Donglu Kunming 650223 Yunnan,China
Tel:+86 871 65130513 Fax:+86 871 65191823 【mail】