Complement C7 is a novel risk gene for Alzheimer's disease in Han Chinese
文献类型：期刊论文
| 作者 | Zhang, Deng-Feng1,2; Fan, Yu1,2; Xu, Min1,3; Wang, Guihong4; Wang, Dong1; Li, Jin5 ; Kong, Li-Li1,3; Zhou, Hejiang1; Luo, Rongcan1,3; Bi, Rui1
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| 刊名 | NATIONAL SCIENCE REVIEW
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| 出版日期 | 2019-03-01 |
| 卷号 | 6期号:2页码:257-274 |
| 关键词 | Alzheimer's disease whole-exome sequencing C7 neuroimaging complement system |
| ISSN号 | 2095-5138 |
| DOI | 10.1093/nsr/nwy127 |
| 通讯作者 | Yao, Yong-Gang(yaoyg@mail.kiz.ac.cn) |
| 英文摘要 | 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. |
| WOS关键词 | GENOME-WIDE ; FUNCTIONAL CONNECTIVITY ; DIAGNOSTIC GUIDELINES ; NATIONAL INSTITUTE ; C7 DEFICIENCY ; HUMAN BRAIN ; ASSOCIATION ; RARE ; VARIANTS ; EXPRESSION |
| 资助项目 | National Natural Science Foundation of China[31730037] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB32020200] ; Bureau of Frontier Sciences and Education, CAS[QYZDJ-SSW-SMC005] ; ADNI (National Institutes of Health)[U01 AG024904] ; Department of Defense[W81XWH-122-0012] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000467957400020 |
| 出版者 | OXFORD UNIV PRESS |
| 资助机构 | National Natural Science Foundation of China ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Bureau of Frontier Sciences and Education, CAS ; ADNI (National Institutes of Health) ; Department of Defense |
| 源URL | [http://ir.ia.ac.cn/handle/173211/24188]  |
| 专题 | 自动化研究所_脑网络组研究中心 |
| 通讯作者 | Yao, Yong-Gang |
| 作者单位 | 1.Chinese Acad Sci, Kunming Inst Zool, Chinese Acad Sci & Yunnan Prov, Key Lab Anim Models & Human Dis Mech, Kunming 650223, Yunnan, Peoples R China 2.Chinese Acad Sci, Ctr Excellence Anim Evolut & Genet, Kunming 650223, Yunnan, Peoples R China 3.Univ Chinese Acad Sci, Kunming Coll Life Sci, Kunming 650204, Yunnan, Peoples R China 4.Capital Med Univ, Beijing Tiantan Hosp, Dept Neurol, Ctr Neurodegenerat Dis, Beijing 100050, Peoples R China 5.Chinese Acad Sci, Inst Automat, Brainnetome Ctr, Beijing 100190, Peoples R China 6.Chinese Acad Sci, Inst Automat, Natl Lab Pattern Recognit, Beijing 100190, Peoples R China 7.Chinese Acad Sci, CAS Ctr Excellence Brain Sci & Intelligence Techn, Shanghai 200031, Peoples R China 8.Kunming Med Univ, Dept Psychiat, Affiliated Hosp 1, Kunming 650032, Yunnan, Peoples R China 9.Cent S Univ, Xiangya Hosp 2, Mental Hlth Inst, Changsha 410011, Hunan, Peoples R China 10.Fudan Univ, Dept Neurol, Zhongshan Hosp, Shanghai 200032, Peoples R China |
| 推荐引用方式 GB/T 7714 | Zhang, Deng-Feng,Fan, Yu,Xu, Min,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, Deng-Feng.,Fan, Yu.,Xu, Min.,Wang, Guihong.,Wang, Dong.,...&Yao, Yong-Gang.(2019).Complement C7 is a novel risk gene for Alzheimer's disease in Han Chinese.NATIONAL SCIENCE REVIEW,6(2),257-274. |
| MLA | Zhang, Deng-Feng,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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来源：自动化研究所
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