TitleWeighted Gene Coexpression Network Analysis Reveals Essential Genes and Pathways in Bipolar Disorder
AuthorsZhang, Zhen-Qing
Wu, Wei-Wei
Chen, Jin-Dong
Zhang, Guang-Yin
Lin, Jing-Yu
Wu, Yan-Kun
Zhang, Yu
Su, Yun-Ai
Li, Ji-Tao
Si, Tian-Mei
AffiliationXiamen Xianyue Hosp, Xiamen, Peoples R China
Peking Univ, Peking Univ Sixth Hosp, Inst Mental Hlth, Beijing, Peoples R China
Tianjin Univ Tradit Chinese Med, Teaching Hosp 1, Dept Psychosomat Med, Tianjin, Peoples R China
Hebei North Univ, Inst Mental Hlth, Zhangjiakou, Hebei, Peoples R China
Issue Date17-Mar-2021
PublisherFRONTIERS IN PSYCHIATRY
AbstractBipolar 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.
URIhttp://hdl.handle.net/20.500.11897/610447
ISSN1664-0640
DOI10.3389/fpsyt.2021.553305
IndexedSCI(E)
SSCI
Appears in Collections:第六医院

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