Sleep Traits and Risk of Epilepsy: A Bidirectional and Multivariable Two-Sample Mendelian Randomization Study

Sleep traits are suggested as risk factors for epilepsy, yet the extent of their shared biological basis and the causal direction between these traits are not well understood. Our goal was to assess the associations and establish causal relationships between sleep traits and epilepsy through Mendelian randomization (MR) analyses.

Univariate and multivariate bidirectional MR analyses were used to assess the causal association between sleep traits and epilepsy. In this study, exposure factors of seven sleep traits and outcome variables related to epilepsy were obtained from the published Genome-Wide Association Study (GWAS). The major analysis utilized for MR was inverse-variance weighted.

Univariable MR analysis indicated that both insomnia and chronotype were positively associated with the risk of generalized epilepsy (GE) [odds ratio (OR)=3.436, 95% confidence interval (CI): 1.081-10.919, p=0.036; OR=1.645, 95% CI: 1.054-2.566, p=0.028]. Additionally, a positive association was found between focal epilepsy (FE) and the risk of daytime napping (OR=1.003, 95% CI: 1.001-1.006, p=0.011). Multivariable MR analysis demonstrated that insomnia was causally and positively linked to GE (OR=5.214, 95% CI: 1.384-19.639, p=0.015). However, after adjusting for other sleep traits and potential confounders, chronotype was found to have no causal effect on GE. Similarly, no causal relationship was found from FE to daytime napping when adjusted for potential confounders.

Our results suggest a shared genetic foundation between sleep traits and epilepsy, indicating potential causal effect of insomnia on GE risk. Interventions targeting sleep disturbances could serve as therapeutic approaches in epilepsy management.