Protein-Protein Interaction and Pathway Analyses of Top Schizophrenia Genes Reveal Schizophrenia Susceptibility Genes Converge on Common Molecular Networks and Enrichment of Nucleosome (Chromatin) Assembly Genes in Schizophrenia Susceptibility Loci
文献类型：期刊论文
| 作者 | Luo XJ[*]1,2; Huang L3,4,5; Zhao ZM6,8,9; Gan L1,2; Jia PL6; Li M7; Su B7 |
| 刊名 | SCHIZOPHRENIA BULLETIN
 |
| 出版日期 | 2014 |
| 卷号 | 40期号:1页码:39-49 |
| 关键词 | genome-wide association study schizophrenia susceptibility genes protein-protein interaction common molecular networks genetic heterogeneity enrichment |
| 通讯作者 | xiongjian_luo@urmc.rochester.edu |
| 英文摘要 | Recent genome-wide association studies have identified many promising schizophrenia candidate genes and demonstrated that common polygenic variation contributes to schizophrenia risk. However, whether these genes represent perturbations to a common but limited set of underlying molecular processes (pathways) that modulate risk to schizophrenia remains elusive, and it is not known whether these genes converge on common biological pathways (networks) or represent different pathways. In addition, the theoretical and genetic mechanisms underlying the strong genetic heterogeneity of schizophrenia remain largely unknown. Using 4 well-defined data sets that contain top schizophrenia susceptibility genes and applying protein-protein interaction (PPI) network analysis, we investigated the interactions among proteins encoded by top schizophrenia susceptibility genes. We found proteins encoded by top schizophrenia susceptibility genes formed a highly significant interconnected network, and, compared with random networks, these PPI networks are statistically highly significant for both direct connectivity and indirect connectivity. We further validated these results using empirical functional data (transcriptome data from a clinical sample). These highly significant findings indicate that top schizophrenia susceptibility genes encode proteins that significantly directly interacted and formed a densely interconnected network, suggesting perturbations of common underlying molecular processes or pathways that modulate risk to schizophrenia. Our findings that schizophrenia susceptibility genes encode a highly interconnected protein network may also provide a novel explanation for the observed genetic heterogeneity of schizophrenia, ie, mutation in any member of this molecular network will lead to same functional consequences that eventually contribute to risk of schizophrenia. |
| 收录类别 | SCI |
| 资助信息 | National Natural Science Foundation of China grants (81271006 to L.G., 81060081 to L.H.); Hangzhou City Health Science Foundation grant (20120633B25 to L.G.); Jiangxi Provincial Natural Science Foundation (2010GZY0089 to L.H.); National Institutes of Health grant (R01LM011177 to Z.Z.); 2010 National Alliance for Research in Schizophrenia and Affective Disorders Young Investigator Award (to P.J.). |
| 语种 | 英语 |
| 源URL | [http://159.226.149.26:8080/handle/152453/10806]  |
| 专题 | 昆明动物研究所_比较基因组学 昆明动物研究所_遗传资源与进化国家重点实验室 昆明动物研究所_转化基因组 |
| 作者单位 | 1.Flaum Eye Institute and Department of Ophthalmology, University of Rochester, Rochester, NY 2.College of Life and Environmental Sciences, Hangzhou Normal University, Hangzhou, Zhejiang, China 3.Medical College of Nanchang University, Nanchang University, Nanchang, Jiangxi, China 4.Department of Ophthalmology, Jiangxi Provincial People’s Hospital, Nanchang, Jiangxi, China 5.First Affiliated Hospital of Gannan Medical University, Gannan Medical University, Ganzhou, Jiangxi, China 6.Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN 7.State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China 8.Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN 9.Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, TN |
| 推荐引用方式 GB/T 7714 | Luo XJ[*],Huang L,Zhao ZM,et al. Protein-Protein Interaction and Pathway Analyses of Top Schizophrenia Genes Reveal Schizophrenia Susceptibility Genes Converge on Common Molecular Networks and Enrichment of Nucleosome (Chromatin) Assembly Genes in Schizophrenia Susceptibility Loci[J]. SCHIZOPHRENIA BULLETIN,2014,40(1):39-49. |
| APA | Luo XJ[*].,Huang L.,Zhao ZM.,Gan L.,Jia PL.,...&Su B.(2014).Protein-Protein Interaction and Pathway Analyses of Top Schizophrenia Genes Reveal Schizophrenia Susceptibility Genes Converge on Common Molecular Networks and Enrichment of Nucleosome (Chromatin) Assembly Genes in Schizophrenia Susceptibility Loci.SCHIZOPHRENIA BULLETIN,40(1),39-49. |
| MLA | Luo XJ[*],et al."Protein-Protein Interaction and Pathway Analyses of Top Schizophrenia Genes Reveal Schizophrenia Susceptibility Genes Converge on Common Molecular Networks and Enrichment of Nucleosome (Chromatin) Assembly Genes in Schizophrenia Susceptibility Loci".SCHIZOPHRENIA BULLETIN 40.1(2014):39-49. |
入库方式： OAI收割
来源：昆明动物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。