Comprehensive integrative analyses identify GLT8D1 and CSNK2B as schizophrenia risk genes.
Cui-Ping YangXiaoyan LiYong WuQiushuo ShenYong ZengQiuxia XiongMengping WeiChunhui ChenJiewei LiuYongxia HuoKaiqin LiGui XueYong-Gang YaoChen ZhangMing LiYongbin ChenXiong-Jian LuoPublished in: Nature communications (2018)
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.
Keyphrases
- genome wide
- bipolar disorder
- genome wide identification
- dna methylation
- genome wide association
- copy number
- bioinformatics analysis
- genome wide analysis
- poor prognosis
- neural stem cells
- spinal cord
- mass spectrometry
- high resolution
- signaling pathway
- big data
- subarachnoid hemorrhage
- climate change
- blood brain barrier