Genetic Insights of Schizophrenia via Single Cell RNA-Sequencing Analyses

	Genetic Insights of Schizophrenia via Single Cell RNA-Sequencing Analyses
	Wu, Y; Zhang, CY; Wang, L; Li, Y; Xiao, X
	2023
发表期刊	SCHIZOPHRENIA BULLETIN
ISSN	0586-7614
卷号	49 期号:4 页码:914-922
摘要	Background Schizophrenia is a complex and heterogeneous disorder involving multiple regions and types of cells in the brain. Despite rapid progress made by genome-wide association studies (GWAS) of schizophrenia, the mechanisms of the illness underlying the GWAS significant loci remain less clear. Study Design We investigated schizophrenia risk genes using summary-data-based Mendelian randomization based on single-cell sequencing data, and explored the types of brain cells involved in schizophrenia through the expression weighted cell-type enrichment analysis. Results We identified 54 schizophrenia risk genes (two-thirds of these genes were not identified using sequencing data of bulk tissues) using single-cell RNA-sequencing data. Further cell type enrichment analysis showed that schizophrenia risk genes were highly expressed in excitatory neurons and caudal ganglionic eminence interneurons, suggesting putative roles of these cells in the pathogenesis of schizophrenia. We also found that these risk genes identified using single-cell sequencing results could form a large protein-protein interaction network with genes affected by disease-causing rare variants. Conclusions Through integrative analyses using expression data at single-cell levels, we identified 54 risk genes associated with schizophrenia. Notably, many of these genes were only identified using single-cell RNA-sequencing data, and their altered expression levels in particular types of cells, rather than in the bulk tissues, were related to the increased risk of schizophrenia. Our results provide novel insight into the biological mechanisms of schizophrenia, and future single-cell studies are necessary to further facilitate the understanding of the disorder.
收录类别	SCI
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/14346
专题	科研部门_环境与精神健康（肖潇）
推荐引用方式 GB/T 7714	Wu, Y,Zhang, CY,Wang, L,et al. Genetic Insights of Schizophrenia via Single Cell RNA-Sequencing Analyses[J]. SCHIZOPHRENIA BULLETIN,2023,49(4):914-922.
APA	Wu, Y,Zhang, CY,Wang, L,Li, Y,&Xiao, X.(2023).Genetic Insights of Schizophrenia via Single Cell RNA-Sequencing Analyses.SCHIZOPHRENIA BULLETIN,49(4),914-922.
MLA	Wu, Y,et al."Genetic Insights of Schizophrenia via Single Cell RNA-Sequencing Analyses".SCHIZOPHRENIA BULLETIN 49.4(2023):914-922.

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