Association Between Sleep Traits and Epilepsy Risk: A Two-Sample Mendelian Randomization Study

Background: Sleep and epilepsy have been reported to have a possible interaction. This study intended to assess the causal relationship between sleep traits and epilepsy risk through a two-sample Mendelian randomization (MR) study. Methods: Exposure- [sleep traits: getting up in morning, sleeplessness/insomnia, sleep duration, nap during day, morning/evening person (chronotype), daytime dozing/sleeping (narcolepsy).] and outcome- [Europeans: epilepsy, focal epilepsy, generalized epilepsy; East Asians: epilepsy] related single-nucleotide polymorphisms (SNPs) from publicly available genome-wide association studies (GWAS) databases were used as instrumental variables for analysis. The main analyses used inverse variance weighted (IVW) to derive causality estimates, which were expressed as odds ratio (OR) and 95% confidence interval (CI). Sensitivity analyses were performed to assess the reliability of the results. Results: For Europeans, genetically predicted getting up in morning decreased the risk of epilepsy (OR=0.354, 95%CI: 0.212-0.589) and generalized epilepsy (OR=0.256, 95%CI: 0.101-0.651), whereas genetically predicted evening person (chronotype) increased the risk of epilepsy (OR=1.371, 95%CI: 1.082-1.739) and generalized epilepsy (OR=1.618, 95%CI: 1.061-2.467). No significant associations were found between genetically predicted sleeplessness/insomnia, sleep duration, nap during day, and daytime dozing/sleeping (narcolepsy) and the risk of epilepsy, focal epilepsy, and generalized epilepsy in Europeans. For East Asians, only genetically predicted sleeplessness/insomnia was found to increase the risk of epilepsy (OR=1.381, 95%CI: 1.039-1.837). Conclusion: There was a causal relationship between getting up in morning and evening person (chronotype) and epilepsy risk in Europeans, and between sleeplessness/insomnia and epilepsy in East Asians.