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Weighted Gene Coexpression Network Analysis Reveals Essential Genes and Pathways in Bipolar Disorder

Bibliographic Data

ID15529623
AuthorsZhenqing Zhang (0000-0003-2820-6775, Peking University Sixth Hospital), Zhen-Qing Zhang, Weiwei Wu (0000-0003-3587-5491, Tianjin haihe hospital), Wei-Wei Wu, Jindong Chen (0000-0003-4551-2344, Tianjin haihe hospital), Jin-Dong Chen, Guang-yin Zhang, Guangyin Zhang (0000-0002-9847-6028, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine), Jingyu Lin (0000-0001-6215-3211, Peking University), Jing-Yu Lin, Yankun Wu (0009-0007-8696-9240, Peking University), Yan-Kun Wu, Yu Zhang (0000-0002-0059-270X, Hebei North University), Yun‐Ai Su (0000-0001-8445-9633, Peking University), Yun-Ai Su, Ji-Tao Li (0000-0003-3160-9225, Peking University Sixth Hospital, corresponding author), Tian-Mei Si (0000-0001-9823-2720, Peking University Sixth Hospital, corresponding author)
Year2021
Volume12
Pages553305-553305
Publication date2021-03-17
Peer ReviewedYes
Open AccessYes
TypeARTICLE
VenueFrontiers in Psychiatry (JOURNAL)
Journal identifiersISSN: 1664-0640 • E-ISSN: 1664-0640
PublisherFrontiers Media (PUBLISHER • CH)
DOI10.3389/fpsyt.2021.553305
PMID33815158
OpenAlexW3136167059
LanguageEN
References cited63

Bipolar disorder (BD) is a major and highly heritable mental illness with severe psychosocial impairment, but its etiology and pathogenesis remains unclear. This study aimed to identify the essential pathways and genes involved in BD using weighted gene coexpression network analysis (WGCNA), a bioinformatic method studying the relationships between genes and phenotypes. Using two available BD gene expression datasets (GSE5388, GSE5389), we constructed a gene coexpression network and identified modules related to BD. The analyses of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways were performed to explore functional enrichment of the candidate modules. A protein-protein interaction (PPI) network was further constructed to identify the potential hub genes. Ten coexpression modules were identified from the top 5,000 genes in 77 samples and three modules were significantly associated with BD, which were involved in several biological processes (e.g., the actin filament-based process) and pathways (e.g., MAPK signaling). Four genes ( NOTCH1, POMC, NGF , and DRD2 ) were identified as candidate hub genes by PPI analysis and CytoHubba. Finally, we carried out validation analyses in a separate dataset, GSE12649, and verified NOTCH1 as a hub gene and the involvement of several biological processes such as actin filament-based process and axon development. Taken together, our findings revealed several candidate pathways and genes ( NOTCH1 ) in the pathogenesis of BD and call for further investigation for their potential research values in BD diagnosis and treatment

Bioinformatics · Biological pathway · Biology · Bipolar disorder · Candidate gene · Computational biology · Gene · Gene expression · Gene ontology · Gene regulatory network · KEGG · Phenotype · Bioinformatics and Genomic Networks · Bipolar Disorder and Treatment · Genetic Associations and Epidemiology · Neuroscience · Genetics

  • Metascape provides a biologist-oriented resource for the analysis of systems-level datasets

    Open Access•Yingyao Zhou, Bin Zhou et al.•Nature Communications•2019

  • Gene Ontology

    Open Access•Michael Ashburner, Catherine A Ball et al.•Nature Genetics•2000

  • Wgcna

    Open Access•Peter Langfelder, Steve Horvath•BMC Bioinformatics•2008

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