Glioblastoma (GBM), a highly aggressive brain tumor predominantly affecting individuals over 40, often co-occurs with sleep disorders. However, the causal relationship remains unclear. This study employed a bidirectional Mendelian randomization (MR) approach to investigate the causal links between sleep traits/disorders and GBM. Sleep trait and disorder data were obtained from the IEU Open GWAS Project, while GBM data came from the Finn cohort. Primary analysis utilized the inverse-variance weighted (IVW) method, complemented by MR-Egger, weighted median, and weighted mode methods. MR pleiotropy residual sum and outlier (MR-PRESSO) was applied to detect potential outliers, and MR-Egger regression explored horizontal pleiotropy, with Cochran'stest assessing heterogeneity. IVW analysis indicated a significant negative association between sleep duration and GBM risk [odds ratio (OR) = 0.13; 95% confidence interval (CI) = 0.02-0.80;= 0.027). Conversely, GBM was positively associated with evening chronotype (OR = 1.0094; 95% CI = 1.0034-1.0154;= 0.002). No significant associations were found for other sleep traits or disorders. Midday napping showed potential pleiotropy, and significant heterogeneity was noted in the reverse analysis. MR-PRESSO identified no outliers. Shorter sleep duration may elevate GBM risk, and GBM might influence circadian preference toward eveningness. Further studies are warranted to validate these findings.This study employs a bidirectional Mendelian randomization approach to explore the causal relationship between various sleep traits, sleep disorders, and glioblastoma (GBM). We found that shorter sleep duration may increase GBM risk, while GBM may shift individuals toward an evening chronotype. No significant relationships were observed for other sleep traits or any of the sleep disorders. These findings illuminate the complex interplay between sleep and GBM, highlighting the need for further investigation into their correlations. Q P P NEW & NOTEWORTHY
