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

Hua Ye1, Shiliang Huang1, Yufei Song1

  • 1Department of Gastroenterology, Ningbo Medical Treatment Center Lihuili Hospital, Medical School of Ningbo University, Ningbo, Zhejiang 315040, PR China.

Sleep Medicine
|August 31, 2021
PubMed
Abstract

Insights

Insufficient sleep disrupts biological rhythms and gene expression, potentially leading to diseases. This study identifies key genes and drugs for sleep disorders using systems biology approaches.

Area of Science:

  • Systems biology
  • Genomics
  • Chronobiology

Background:

  • Insufficient sleep and circadian rhythm disruption are linked to severe health issues, including cancer, obesity, cardiovascular disease, and cognitive impairment.
  • The precise biological mechanisms underlying these associations require further investigation.

Purpose of the Study:

  • To elucidate the molecular mechanisms connecting insufficient sleep and circadian rhythm disruption to disease.
  • To identify key genes, biological modules, and potential therapeutic drugs associated with sleep disorders.

Main Methods:

  • Weighted gene co-expression network analysis (WGCNA) to identify gene modules.
  • Connectivity Map tool for drug discovery based on hub genes.
  • R ptestg package and hypergeometric tests to analyze module rhythmicity and genetic associations (GWAS).

Main Results:

  • Identified 45 stable co-expressed gene modules, with eight significantly correlated with sleep restriction duration.
  • Demonstrated disrupted module rhythmicity in subjects with insufficient sleep.
  • Found enrichment of insomnia GWAS signals in six modules and identified eight candidate drugs for sleep disorders.

Conclusions:

  • Systems biology approaches effectively identified sleep-related gene modules, hub genes, and potential therapeutic targets.
  • Altered module rhythmicity is a key indicator of sleep insufficiency.
  • Thiamphenicol, lisuride, timolol, and piretanide represent novel therapeutic candidates for sleep disorders.
Keywords:
Gene modulesHubsSNPsTranscriptome

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