Complement C7 is a novel risk gene for Alzheimer's disease in Han Chinese

	Complement C7 is a novel risk gene for Alzheimer's disease in Han Chinese
	Zhang, DF; Fan, Y; Xu, M; Wang, GH; Wang, D; Li, J; Kong, LL; Zhou, HJ; Luo, RC; Bi, R; Wu, Y; Li, GD; Li, M; Luo, XJ; Jiang, HY; Tan, LW; Zhong, CJ; Fang, YR; Zhang, C; Sheng, NY; Jiang, TZ; Yao, YG
	2019
发表期刊	NATIONAL SCIENCE REVIEW
ISSN	2095-5138
卷号	6 期号:2 页码:257-274
摘要	Alzheimer's disease is the most common neurodegenerative disease, and has a high level of genetic heritability and population heterogeneity. In this study, we performed the whole-exome sequencing of Han Chinese patients with familial and/or early-onset Alzheimer's disease, followed by independent validation, imaging analysis and function characterization. We identified an exome-wide significant rare missense variant rs3792646 (p.K420Q) in the C7 gene in the discovery stage (P = 1.09 x 10(-6), odds ratio = 7.853) and confirmed the association in different cohorts and a combined sample (1615 cases and 2832 controls, P-combined = 2.99 x 10(-7), odds ratio = 1.930). The risk allele was associated with decreased hippocampal volume and poorer working memory performance in early adulthood, thus resulting in an earlier age of disease onset. Overexpression of the mutant p.K420Q disturbed cell viability, immune activation and beta-amyloid processing. Electrophysiological analyses showed that the mutant p.K420Q impairs the inhibitory effect of wild type C7 on the excitatory synaptic transmission in pyramidal neurons. These findings suggested that C7 is a novel risk gene for Alzheimer's disease in Han Chinese.
收录类别	SCIE
语种	英语
文献类型	期刊论文
条目标识符	http://ir.kiz.ac.cn/handle/152453/12456
专题	科研部门_神经系统疾病（罗雄剑）昆明动物研究所科研部门_疾病机理遗传学和进化医学学科组（姚永刚）
推荐引用方式 GB/T 7714	Zhang, DF,Fan, Y,Xu, M,et al. Complement C7 is a novel risk gene for Alzheimer's disease in Han Chinese[J]. NATIONAL SCIENCE REVIEW,2019,6(2):257-274.
APA	Zhang, DF.,Fan, Y.,Xu, M.,Wang, GH.,Wang, D.,...&Yao, YG.(2019).Complement C7 is a novel risk gene for Alzheimer's disease in Han Chinese.NATIONAL SCIENCE REVIEW,6(2),257-274.
MLA	Zhang, DF,et al."Complement C7 is a novel risk gene for Alzheimer's disease in Han Chinese".NATIONAL SCIENCE REVIEW 6.2(2019):257-274.

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