Causal Association Between Sleep Deprivation and Glioblastoma Risk: Insights from Multi-Omics Analysis

Area of Science:

• Neuro-oncology
• Sleep Medicine
• Genetics

Background:

• Emerging evidence links sleep deprivation to cancer risk.
• The genetic association between sleep traits and glioblastoma (GBM) is not well understood.

Purpose of the Study:

• To investigate the potential causal relationship between sleep duration, sleeplessness, and GBM risk.
• To identify immune mediators involved in the sleep-GBM association.
• To explore molecular changes in the brain associated with sleep deprivation and GBM.

Main Methods:

• Mendelian randomization (MR) analyses using GWAS data from UK Biobank and FinnGen.
• Mediation analysis to identify immune cell mediators.
• Single-nucleus RNA sequencing (snRNA-seq) and transcriptomic analysis in mouse models of sleep deprivation.

Main Results:

• Reduced sleep duration showed a significant causal association with increased GBM risk (OR = 6.000 × 10^-5, P = 0.003).
• Sleeplessness was also identified as a potential GBM risk factor (OR = 20.221).
• CD80 expression on plasmacytoid dendritic cells (pDCs) was identified as a mediator (effect = 0.256), with significant alterations observed in sleep-deprived mice.
• Upregulation of GBM-related markers (Egfr, Tert, Mgmt) and pathways was observed in sleep-deprived mouse brains.

Conclusions:

• Findings suggest a potential causal link between insufficient sleep and elevated GBM risk.
• Sleep management may be crucial for GBM prevention and patient care.
• Immune dysregulation, particularly involving CD80+ pDCs, may mediate the effects of sleep deprivation on GBM development.