Gene co-expression analysis identifies modules related to insufficient sleep in humans

• Published in: Sleep medicine Vol. 86; pp. 68 - 74
• Main Authors: Ye, Hua, Huang, Shiliang, Song, Yufei, Liu, Huiwei, Zhao, Xiaosu, Zhao, Dan, Mi, Fangxia, Wang, Xinxue, Zhang, Xuesong, Du, Jinman, Zhu, Na, Zhang, Liangshun, Zhao, Yibin
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 01.10.2021
• Subjects: Gene modules; Hubs; SNPs; Transcriptome; Gene modules; SNPs; Hubs; Transcriptome
• ISSN: 1389-9457; 1878-5506; 1878-5506
• DOI: 10.1016/j.sleep.2021.08.010

Insufficient sleep and circadian rhythm disruption may cause cancer, obesity, cardiovascular disease, and cognitive impairment. The underlying mechanisms need to be elucidated. Weighted gene co-expression network analysis (WGCNA) was used to identify co-expressed modules. Connectivity Map tool was used to identify candidate drugs based on top connected genes. R ptestg package was utilized to detected module rhythmicity alteration. A hypergeometric test was used to test the enrichment of insomnia SNP signals in modules. Google Scholar was used to validate the modules and hub genes by literature. We identified a total of 45 co-expressed modules. These modules were stable and preserved. Eight modules were correlated with sleep restriction duration. Module rhythmicity was disrupted in sleep restriction subjects. Hub genes that involve in insufficient sleep also play important roles in sleep disorders. Insomnia GWAS signals were enriched in six modules. Finally, eight drugs associated with sleep disorders were identified. Systems biology method was used to identify sleep-related modules, hub genes, and candidate drugs. Module rhythmicity was altered in sleep insufficient subjects. Thiamphenicol, lisuride, timolol, and piretanide are novel candidates for sleep disorders. •Weighted gene co-expression network analysis (WGCNA) was applied to insufficient sleep human blood transcriptome.•45 biological meaningful modules were identified. Insomnia GWAS signals were enriched in six modules.•Module rhythmicity was disrupted in sleep restriction subjects.•Hub genes, such as CACNB3, UFL1 and DPM2, involved in insufficient sleep may also play important roles in sleep disorders.•Eight drugs associated with sleep disorders were identified.