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

Nov 25, 2025Yonsei medical journal

Sleep characteristics may influence the risk of epilepsy and vice versa.

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Abstract

Insomnia is positively associated with a 5.214 times increased risk of .

Univariable analysis found insomnia and chronotype both linked to increased risk of generalized epilepsy.
The odds ratio for insomnia related to generalized epilepsy was 3.436, while for chronotype it was 1.645.
Daytime napping showed a positive association with focal epilepsy, with an odds ratio of 1.003.
Multivariable analysis indicated a causal link between insomnia and generalized epilepsy but not for chronotype.
No causal relationship was identified between focal epilepsy and daytime napping after adjusting for confounders.

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PURPOSE: 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 (MR) analyses.

MATERIALS AND METHODS: 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.

RESULTS: Univariable MR analysis indicated that both insomnia and chronotype were positively associated with the risk of (GE) [odds ratio (OR)=3.436, 95% confidence interval (CI): 1.081-10.919,=0.036; OR=1.645, 95% CI: 1.054-2.566,=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,=0.011). Multivariable MR analysis demonstrated that insomnia was causally and positively linked to GE (OR=5.214, 95% CI: 1.384-19.639,=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. p p p p

CONCLUSION: 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.

Key numbers

3.436

Odds Ratio for insomnia and

263615 to 476853

Sample sizes for sleep traits

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

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