CASIA OpenIR
Complement C7 is a novel risk gene for Alzheimer's disease in Han Chinese
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; Wu, Yong1,3; Li, Guo-Dong1,3; Li, Ming1,7; Luo, Xiong-Jian1,2; Jiang, Hong-Yan8; Tan, Liwen9; Zhong, Chunjiu10; Fang, Yiru11; Zhang, Chen11; Sheng, Nengyin2,12; Jiang, Tianzi5,6,7; Yao, Yong-Gang1,3,7,13
Source PublicationNATIONAL SCIENCE REVIEW
ISSN2095-5138
2019-03-01
Volume6Issue:2Pages:257-274
Corresponding AuthorYao, Yong-Gang(yaoyg@mail.kiz.ac.cn)
AbstractAlzheimer'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.
KeywordAlzheimer's disease whole-exome sequencing C7 neuroimaging complement system
DOI10.1093/nsr/nwy127
WOS KeywordGENOME-WIDE ; FUNCTIONAL CONNECTIVITY ; DIAGNOSTIC GUIDELINES ; NATIONAL INSTITUTE ; C7 DEFICIENCY ; HUMAN BRAIN ; ASSOCIATION ; RARE ; VARIANTS ; EXPRESSION
Indexed BySCI
Language英语
Funding ProjectNational 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]
Funding OrganizationNational 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
WOS Research AreaScience & Technology - Other Topics
WOS SubjectMultidisciplinary Sciences
WOS IDWOS:000467957400020
PublisherOXFORD UNIV PRESS
Citation statistics
Cited Times:3[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ia.ac.cn/handle/173211/24189
Collection中国科学院自动化研究所
Corresponding AuthorYao, Yong-Gang
Affiliation1.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
11.Shanghai Jiao Tong Univ, Shanghai Mental Hlth Ctr, Div Mood Disorders, Sch Med, Shanghai 200030, Peoples R China
12.Chinese Acad Sci, State Key Lab Genet Resources & Evolut, Kunming Inst Zool, Kunming 650223, Yunnan, Peoples R China
13.Chinese Acad Sci, Kunming Inst Zool, KIZ CUHK Joint Lab Bioresources & Mol Res Common, Kunming 650223, Yunnan, Peoples R China
Recommended Citation
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.
Files in This Item:
There are no files associated with this item.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Zhang, Deng-Feng]'s Articles
[Fan, Yu]'s Articles
[Xu, Min]'s Articles
Baidu academic
Similar articles in Baidu academic
[Zhang, Deng-Feng]'s Articles
[Fan, Yu]'s Articles
[Xu, Min]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Zhang, Deng-Feng]'s Articles
[Fan, Yu]'s Articles
[Xu, Min]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.