Causal Associations between Sleep Traits, Sleep Disorders, and Glioblastoma: A Two-Sample Bidirectional Mendelian Randomization Study

This study applied Mendelian Randomization (MR) analysis to investigate the bidirectional causal association of sleep traits (chronotype, getting up in the morning, midday nap, sleep duration, and sleep episodes) and sleep disorders (insomnia, narcolepsy, sleep apnea, and general sleep disorders) with GBM, based on their potential links with GBM.
Study design and data source
GWAS data for GBM was sourced from genome sequencing data of the Finn cohort. Data regarding sleep traits and sleep disorders were collected from the UKB and GWAS Catalog, with sample sizes ranging from 84,810 to 462,400 (Table S1).
MR analysis
A bidirectional MR approach was used to investigate the causal associations between sleep traits, sleep disorders, and GBM.
Sensitivity analysis
Sensitivity analysis was conducted to detect potential heterogeneity in MR studies. Cochran's Q test was used to assess heterogeneity among IVs, with P > 0.05 indicating low heterogeneity, meaning the estimates among instrumental variables were randomly distributed and had little impact on IVW results. Considering the potential impact of genetic variation on the estimation of association effects, this study used the MR-Egger regression method to explore the presence of horizontal pleiotropy; when the intercept of MR-Egger regression approaches zero or is not statistically significant, it suggests the absence of pleiotropy. Additionally, the MR pleiotropy residual sum and outlier (MR-PRESSO) method was used to detect potential outliers (i.e., SNPs with P < 0.05) and re-estimate causal associations after their removal to correct for horizontal pleiotropy. Leave-one-out analysis was employed to assess the robustness and consistency of the results.
RESULTS
The causal effects of sleep traits and sleep disorders on GBM
First, we assessed the causal effects of sleep traits and sleep disorders on GBM risk. For sleep traits, 152 IVs were selected for chronotype, 73 for getting up in the morning, 84 for a midday nap, 68 for sleep duration, and 20 for sleep episodes. For sleep disorders, 39 IVs were selected for insomnia, 30 for narcolepsy, 16 for sleep apnea, and 27 for general sleep disorders. The F values are shown in Table S2. No associations were found between other sleep traits or any of the sleep disorders and GBM (all P > 0.05) (Figure S1-4).
The causal effect of GBM on sleep traits and sleep disorders
The causal effects of GBM on sleep traits and sleep disorders were assessed. A total of 4 IVs were selected; the F values are shown in Table S2. No association was found when MR Egger and Weighted mode were applied (both P > 0.05), while WM showed statistical significance (OR: 1.0085, 95% CI: 1.0011 - 1.0159, P = 0.024). There was no association between GBM and other sleep traits and sleep disorders (all P > 0.05) (Figure S5-8).