Regulatory Variant rs2535629 in ITIH3 Intron Confers Schizophrenia Risk By Regulating CTCF Binding and SFMBT1 Expression

	Regulatory Variant rs2535629 in ITIH3 Intron Confers Schizophrenia Risk By Regulating CTCF Binding and SFMBT1 Expression
	Li, YF; Ma, CG; Li, SW; Wang, JY; Li, WQ; Yang, YF; Li, XY; Liu, JW; Yang, JF; Liu, YX; Li, KQ; Li, J; Huang, D; Chen, R; Lv, LX; Xiao, X; Li, M; Luo, XJ
	2022
发表期刊	ADVANCED SCIENCE
卷号	9 期号:6
摘要	Genome-wide association studies have identified 3p21.1 as a robust risk locus for schizophrenia. However, the underlying molecular mechanisms remain elusive. Here a functional regulatory variant (rs2535629) is identified that disrupts CTCF binding at 3p21.1. It is confirmed that rs2535629 is also significantly associated with schizophrenia in Chinese population and the regulatory effect of rs2535629 is validated. Expression quantitative trait loci analysis indicates that rs2535629 is associated with the expression of three distal genes (GLT8D1, SFMBT1, and NEK4) in the human brain, and CRISPR-Cas9-mediated genome editing confirmed the regulatory effect of rs2535629 on GLT8D1, SFMBT1, and NEK4. Interestingly, differential expression analysis of GLT8D1, SFMBT1, and NEK4 suggested that rs2535629 may confer schizophrenia risk by regulating SFMBT1 expression. It is further demonstrated that Sfmbt1 regulates neurodevelopment and dendritic spine density, two key pathological characteristics of schizophrenia. Transcriptome analysis also support the potential role of Sfmbt1 in schizophrenia pathogenesis. The study identifies rs2535629 as a plausibly causal regulatory variant at the 3p21.1 risk locus and demonstrates the regulatory mechanism and biological effect of this functional variant, indicating that this functional variant confers schizophrenia risk by altering CTCF binding and regulating expression of SFMBT1, a distal gene which plays important roles in neurodevelopment and synaptic morphogenesis.
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/152453/13329
专题	科研部门_神经系统疾病（罗雄剑）
推荐引用方式 GB/T 7714	Li, YF,Ma, CG,Li, SW,et al. Regulatory Variant rs2535629 in ITIH3 Intron Confers Schizophrenia Risk By Regulating CTCF Binding and SFMBT1 Expression[J]. ADVANCED SCIENCE,2022,9(6).
APA	Li, YF.,Ma, CG.,Li, SW.,Wang, JY.,Li, WQ.,...&Luo, XJ.(2022).Regulatory Variant rs2535629 in ITIH3 Intron Confers Schizophrenia Risk By Regulating CTCF Binding and SFMBT1 Expression.ADVANCED SCIENCE,9(6).
MLA	Li, YF,et al."Regulatory Variant rs2535629 in ITIH3 Intron Confers Schizophrenia Risk By Regulating CTCF Binding and SFMBT1 Expression".ADVANCED SCIENCE 9.6(2022).

条目包含的文件
文件名称/大小	文献类型	版本类型	开放类型	使用许可
2023032111.pdf（6866KB）	期刊论文	出版稿	开放获取	CC BY-NC-SA	请求全文