Unraveling NEK4 as a Potential Drug Target in Schizophrenia and Bipolar I Disorder: A Proteomic and Genomic Approach

	Unraveling NEK4 as a Potential Drug Target in Schizophrenia and Bipolar I Disorder: A Proteomic and Genomic Approach
	Zhang, CC; Yang, ZH; Li, XJ; Zhao, LS; Guo, WJ; Deng, W; Wang, Q; Hu, X; Li, M; Sham, PC; Xiao, X; Li, T
	2024
发表期刊	SCHIZOPHRENIA BULLETIN
ISSN	0586-7614
摘要	Background and Hypothesis Investigating the shared brain protein and genetic components of schizophrenia (SCZ) and bipolar I disorder (BD-I) presents a unique opportunity to understand the underlying pathophysiological processes and pinpoint potential drug targets.Study Design To identify overlapping susceptibility brain proteins in SCZ and BD-I, we carried out proteome-wide association studies (PWAS) and Mendelian Randomization (MR) by integrating human brain protein quantitative trait loci with large-scale genome-wide association studies for both disorders. We utilized transcriptome-wide association studies (TWAS) to determine the consistency of mRNA-protein dysregulation in both disorders. We applied pleiotropy-informed conditional false discovery rate (pleioFDR) analysis to identify common risk genetic loci for SCZ and BD-I. Additionally, we performed a cell-type-specific analysis in the human brain to detect risk genes notably enriched in distinct brain cell types. The impact of risk gene overexpression on dendritic arborization and axon length in neurons was also examined.Study Results Our PWAS identified 42 proteins associated with SCZ and 14 with BD-I, among which NEK4, HARS2, SUGP1, and DUS2 were common to both conditions. TWAS and MR analysis verified the significant risk gene NEK4 for both SCZ and BD-I. PleioFDR analysis further supported genetic risk loci associated with NEK4 for both conditions. The cell-type specificity analysis revealed that NEK4 is expressed on the surface of glutamatergic neurons, and its overexpression enhances dendritic arborization and axon length in cultured primary neurons.Conclusions These findings underscore a shared genetic origin for SCZ and BD-I, offering novel insights for potential therapeutic target identification.
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/152453/14342
专题	科研部门_环境与精神健康（肖潇）
推荐引用方式 GB/T 7714	Zhang, CC,Yang, ZH,Li, XJ,et al. Unraveling NEK4 as a Potential Drug Target in Schizophrenia and Bipolar I Disorder: A Proteomic and Genomic Approach[J]. SCHIZOPHRENIA BULLETIN,2024.
APA	Zhang, CC.,Yang, ZH.,Li, XJ.,Zhao, LS.,Guo, WJ.,...&Li, T.(2024).Unraveling NEK4 as a Potential Drug Target in Schizophrenia and Bipolar I Disorder: A Proteomic and Genomic Approach.SCHIZOPHRENIA BULLETIN.
MLA	Zhang, CC,et al."Unraveling NEK4 as a Potential Drug Target in Schizophrenia and Bipolar I Disorder: A Proteomic and Genomic Approach".SCHIZOPHRENIA BULLETIN (2024).

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