Comprehensive integrative analyses identify GLT8D1 and CSNK2B as schizophrenia risk genes. Nat Commun, 2018, 9(1): 838

Title:  Comprehensive integrative analyses identify GLT8D1 and CSNK2B as schizophrenia risk genes.  

Author:  Yang CP, Li X, Wu Y, Shen Q, Zeng Y, Xiong Q, Wei M, Chen C, Liu J, Huo Y, Li K, Xue G, Yao YG, Zhang C, Li M, Chen Y, Luo XJ

Pub Year: 2018

Publication Name: Nat Commun

Volume: 9

Issue: 1

Page Number: 838

IF: 12.353

Abstract:

Recent genome-wide association studies (GWAS) have identified multiple risk loci that show strong associations with schizophrenia. However, pinpointing the potential causal genes at the reported loci remains a major challenge. Here we identify candidate causal genes for schizophrenia using an integrative genomic approach. Sherlock integrative analysis shows that ALMS1, GLT8D1, and CSNK2B are schizophrenia risk genes, which are validated using independent brain expression quantitative trait loci (eQTL) data and integrative analysis method (SMR). Consistently, gene expression analysis in schizophrenia cases and controls further supports the potential role of these three genes in the pathogenesis of schizophrenia. Finally, we show that GLT8D1 and CSNK2B knockdown promote the proliferation and inhibit the differentiation abilities of neural stem cells, and alter morphology and synaptic transmission of neurons. These convergent lines of evidence suggest that the ALMS1, CSNK2B, and GLT8D1 genes may be involved in pathophysiology of schizophrenia.