CASIA OpenIR
A Schizophrenia-Related Genetic-Brain-Cognition Pathway Revealed in a Large Chinese Population
Luo, Na1,2,3; Sui, Jing1,2,3,4,5,20; Chen, Jiayu4,5; Zhang, Fuquan6; Tian, Lin6; Lin, Dongdong4,5; Song, Ming1,2,3; Calhoun, Vince D.4,5,19; Cui, Yue1,2,3; Vergara, Victor M.4,5; Zheng, Fanfan1,2,3; Liu, Jingyu4,5; Yang, Zhenyi1,2,3; Zuo, Nianming1,2,3; Fan, Lingzhong1,2,3; Xu, Kaibin1,2,3; Liu, Shengfeng1,2,3; Li, Jian1,2,3; Xu, Yong7; Liu, Sha7; Lv, Luxian8,9; Chen, Jun10; Chen, Yunchun11; Guo, Hua12; Li, Peng13,14; Lu, Lin13,14; Wan, Ping12; Wang, Huaning11; Wang, Huiling10; Yan, Hao13,14; Yan, Jun13,14; Yang, Yongfeng8,9,17; Zhang, Hongxing8,15; Zhang, Dai13,14,16; Jiang, Tianzi1,2,3,17,18,20
Source PublicationEBIOMEDICINE
ISSN2352-3964
2018-11-01
Volume37Pages:471-482
Corresponding AuthorSui, Jing(jing.sui@nlpr.ia.ac.cn) ; Jiang, Tianzi(jiangtz@nlpr.ia.ac.cn)
AbstractBackground: In the past decades, substantial effort has been made to explore the genetic influence on brain structural/functional abnormalities in schizophrenia, as well as cognitive impairments. In this work, we aimed to extend previous studies to explore the internal mediation pathway among genetic factor, brain features and cognitive scores in a large Chinese dataset. Methods: Gray matter (GM) volume, fractional amplitude of low-frequency fluctuations (fALFF), and 4522 schizophrenia-susceptible single nucleotide polymorphisms (SNP) from 905 Chinese subjects were jointly analyzed, to investigate the multimodal association. Based on the identified imaging-genetic pattern, correlations with cognition and mediation analysis were then conducted to reveal the potential mediation pathways. Findings: One linked imaging-genetic pattern was identified to be group discriminative, which was also associated with working memory performance. Particularly, GM reduction in thalamus, putamen and bilateral temporal gyrus in schizophrenia was associated with fALFF decrease in medial prefrontal cortex, both were also associated with genetic factors enriched in neuron development, synapse organization and axon pathways, highlighting genes including CSMD1, CNTNAP2, DCC, GABBR2 etc. This linked pattern was also replicated in an independent cohort (166 subjects), which although showed certain age and clinical differences with the discovery cohort. A further mediation analysis suggested that GM alterations significantly mediated the association from SNP to fALFF, while fALFF mediated the association from SNP and GM to working memory performance. Interpretation: This study has not only verified the impaired imaging-genetic association in schizophrenia,but also initially revealed a potential genetic-brain-cognition mediation pathway, indicating that polygenic risk factors could exert impact on phenotypic measures from brain structure to function, thus could further affect cognition in schizophrenia. (C) 2018 The Authors. Published by Elsevier B.V.
KeywordSchizophrenia Multimodal fusion Genetic-brain-cognition pathway Working memory Mediation analysis
DOI10.1016/j.ebiom.2018.10.009
WOS KeywordINDEPENDENT COMPONENT ANALYSIS ; GRAY-MATTER ABNORMALITIES ; FUNCTIONAL CONNECTIVITY ; MULTIMODAL FUSION ; TEMPORAL GYRUS ; GENOMIC RISK ; ASSOCIATION ; MEMORY ; VOLUME ; LOCI
Indexed BySCI
Language英语
Funding ProjectNatural Science Foundation of China[81471367] ; Natural Science Foundation of China[61773380] ; Natural Science Foundation of China[31771076] ; Natural Science Foundation of China[91432302] ; Natural Science Foundation of China[91732305] ; Natural Science Foundation of China[31620103905] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDBS01040100] ; Science Frontier Program of the Chinese Academy of Sciences[QYZDJ-SSW-SMC019] ; National Key R&D Program of China[2017YFA0105203] ; Primary Research & Development Plan of Jiangsu Province[BE2016630] ; National Institute of Health[R56MH117107] ; National Institute of Health[R01EB005846] ; National Institute of Health[R01MH094524] ; National Institute of Health[P20GM103472] ; National Science Foundation[1539067]
Funding OrganizationNatural Science Foundation of China ; Strategic Priority Research Program of the Chinese Academy of Sciences ; Science Frontier Program of the Chinese Academy of Sciences ; National Key R&D Program of China ; Primary Research & Development Plan of Jiangsu Province ; National Institute of Health ; National Science Foundation
WOS Research AreaGeneral & Internal Medicine ; Research & Experimental Medicine
WOS SubjectMedicine, General & Internal ; Medicine, Research & Experimental
WOS IDWOS:000451691900060
PublisherELSEVIER SCIENCE BV
Citation statistics
Cited Times:2[WOS]   [WOS Record]     [Related Records in WOS]
Document Type期刊论文
Identifierhttp://ir.ia.ac.cn/handle/173211/25696
Collection中国科学院自动化研究所
Corresponding AuthorSui, Jing; Jiang, Tianzi
Affiliation1.Chinese Acad Sci, Inst Automat, Brainnetome Ctr, Beijing 100190, Peoples R China
2.Chinese Acad Sci, Inst Automat, Natl Lab Pattern Recognit, Beijing 100190, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.Mind Res Network, Albuquerque, NM 87106 USA
5.LBERI, Albuquerque, NM 87106 USA
6.Wuxi Menial Hlth Ctr, Wuxi 214000, Peoples R China
7.Shanxi Med Univ, Clin Med Coll 1, Dept Psychiat, Hosp 1, Taiyuan 030000, Shanxi, Peoples R China
8.Xinxiang Med Univ, Dept Psychiat, Henan Mental Hosp, Affiliated Hosp 2, Xinxiang 453002, Peoples R China
9.Xinxiang Med Univ, Henan Key Lab Biol Psychiat, Xinxiang 453002, Peoples R China
10.Wuhan Univ, Dept Radiol, Renmin Hosp, Wuhan 430060, Hubei, Peoples R China
11.Fourth Mil Med Univ, Xijing Hosp, Dept Psychiat, Xian 710032, Shaanxi, Peoples R China
12.Zhumadian Psychiat Hosp, Zhumadian 463000, Peoples R China
13.Peking Univ, Inst Mental Hlth, Hosp 6, Beijing 100191, Peoples R China
14.Peking Univ, Key Lab Mental Hlth, Minist Hlth, Beijing 100191, Peoples R China
15.Xinxiang Med Univ, Dept Psychol, Xinxiang 453002, Peoples R China
16.Peking Univ, Ctr Life Sci, PKU IDG, McGovern Inst Brain Res, Beijing 100871, Peoples R China
17.Univ Elect Sci & Technol China, Key Lab NeuroInformat, Minist Educ, Sch Life Sci & Technol, Chengdu 610054, Sichuan, Peoples R China
18.Univ Queensland, Queensland Brain Inst, Brisbane, Qld 4072, Australia
19.Univ New, Dept Elect & Comp Engineer, Albuquerque, NM 87131 USA
20.Chinese Acad Sci, CAS Ctr Excellence Brain Sci & Intelligence Techn, Inst Automat, Beijing 100190, Peoples R China
First Author AffilicationInstitute of Automation, Chinese Academy of Sciences;  Chinese Acad Sci, Inst Automat, Natl Lab Pattern Recognit, Beijing 100190, Peoples R China
Corresponding Author AffilicationInstitute of Automation, Chinese Academy of Sciences;  Chinese Acad Sci, Inst Automat, Natl Lab Pattern Recognit, Beijing 100190, Peoples R China
Recommended Citation
GB/T 7714
Luo, Na,Sui, Jing,Chen, Jiayu,et al. A Schizophrenia-Related Genetic-Brain-Cognition Pathway Revealed in a Large Chinese Population[J]. EBIOMEDICINE,2018,37:471-482.
APA Luo, Na.,Sui, Jing.,Chen, Jiayu.,Zhang, Fuquan.,Tian, Lin.,...&Jiang, Tianzi.(2018).A Schizophrenia-Related Genetic-Brain-Cognition Pathway Revealed in a Large Chinese Population.EBIOMEDICINE,37,471-482.
MLA Luo, Na,et al."A Schizophrenia-Related Genetic-Brain-Cognition Pathway Revealed in a Large Chinese Population".EBIOMEDICINE 37(2018):471-482.
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