Comprehensive integrative analyses identify GLT8D1 and CSNK2B as schizophrenia risk genes

Nature Communications
Cui-Ping YangXiong-Jian Luo

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.

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Citations

Nov 10, 2018·Genes, Brain, and Behavior·Jan VeveraStanislav Kmoch
Feb 17, 2019·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Jingmei ZhongXiong-Jian Luo
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Sep 10, 2020·Journal of Medical Genetics·Yan ZhangXiongJian Luo

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Datasets Mentioned

BETA
GSE12649
GSE53987
40
AB5622

Methods Mentioned

BETA
PCR
genotyping
transfection

Software Mentioned

ENIGMA
Matrix eQTL
Clampfit
ggplot2
GTEx
DAPPLE
Igor
PLINK
CFG
Sherlock

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