Causal Relationship Between Epilepsy, Status Epilepticus and Sleep-Related Traits: A Bidirectional Mendelian Randomization Study

<b>Background/Objectives</b>: Epilepsy and sleep disturbances frequently co-occur, yet the causal nature of this relationship remains uncertain, particularly in relation to epilepsy subtypes and status epilepticus. We investigated potential bidirectional causal associations between sleep...

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Main Authors: Yong-Won Shin, Sang Bin Hong
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Brain Sciences
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Online Access:https://www.mdpi.com/2076-3425/15/7/749
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author Yong-Won Shin
Sang Bin Hong
author_facet Yong-Won Shin
Sang Bin Hong
author_sort Yong-Won Shin
collection DOAJ
description <b>Background/Objectives</b>: Epilepsy and sleep disturbances frequently co-occur, yet the causal nature of this relationship remains uncertain, particularly in relation to epilepsy subtypes and status epilepticus. We investigated potential bidirectional causal associations between sleep-related traits and epilepsy, including subtypes and status epilepticus, using Mendelian randomization (MR). <b>Methods</b>: We conducted two-sample MR using genome-wide association study (GWAS) summary statistics from European ancestry cohorts. Epilepsy, its subtypes, and status epilepticus were analyzed using data from the International League Against Epilepsy Consortium on Complex Epilepsies (ILAE) and the FinnGen study. Nine self-reported sleep-related traits were derived from the UK Biobank-based GWAS. Causal estimates were primarily obtained using inverse variance weighted models with additional MR analysis methods. Pleiotropy and heterogeneity were assessed to enhance the robustness of the finding. <b>Results</b>: Several subtype-specific associations were identified, with direction and statistical significance varying across cohorts and subtypes. After correction for multiple testing and filtering for tests with ≥10 instrumental variables to ensure robust and reliable MR estimates, several consistent and potentially mutually reinforcing associations emerged. In the ILAE cohort, focal epilepsy with hippocampal sclerosis was associated with an increased risk of insomnia, and juvenile myoclonic epilepsy with reduced sleep duration. In the FinnGen cohort, overall epilepsy was associated with increased risk of both insomnia and daytime sleepiness. In reverse MR, daytime sleepiness and napping were associated with increased risk of epilepsy, while daytime napping and frequent insomnia symptoms were linked to elevated risk of status epilepticus. <b>Conclusions</b>: Our findings reveal subtype-specific and bidirectional causal links between epilepsy and sleep-related traits. These results highlight the biological interplay between epileptic networks and sleep regulation and underscore the need for further clinical and mechanistic studies.
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spelling doaj-art-f1a0c2a91ed64ee99d70a4b49b91bab82025-07-25T13:17:08ZengMDPI AGBrain Sciences2076-34252025-07-0115774910.3390/brainsci15070749Causal Relationship Between Epilepsy, Status Epilepticus and Sleep-Related Traits: A Bidirectional Mendelian Randomization StudyYong-Won Shin0Sang Bin Hong1Department of Critical Care Medicine, Seoul National University Hospital, Seoul 03080, Republic of KoreaCenter for Hospital Medicine, Department of Neurology, Seoul National University Hospital, Seoul 03080, Republic of Korea<b>Background/Objectives</b>: Epilepsy and sleep disturbances frequently co-occur, yet the causal nature of this relationship remains uncertain, particularly in relation to epilepsy subtypes and status epilepticus. We investigated potential bidirectional causal associations between sleep-related traits and epilepsy, including subtypes and status epilepticus, using Mendelian randomization (MR). <b>Methods</b>: We conducted two-sample MR using genome-wide association study (GWAS) summary statistics from European ancestry cohorts. Epilepsy, its subtypes, and status epilepticus were analyzed using data from the International League Against Epilepsy Consortium on Complex Epilepsies (ILAE) and the FinnGen study. Nine self-reported sleep-related traits were derived from the UK Biobank-based GWAS. Causal estimates were primarily obtained using inverse variance weighted models with additional MR analysis methods. Pleiotropy and heterogeneity were assessed to enhance the robustness of the finding. <b>Results</b>: Several subtype-specific associations were identified, with direction and statistical significance varying across cohorts and subtypes. After correction for multiple testing and filtering for tests with ≥10 instrumental variables to ensure robust and reliable MR estimates, several consistent and potentially mutually reinforcing associations emerged. In the ILAE cohort, focal epilepsy with hippocampal sclerosis was associated with an increased risk of insomnia, and juvenile myoclonic epilepsy with reduced sleep duration. In the FinnGen cohort, overall epilepsy was associated with increased risk of both insomnia and daytime sleepiness. In reverse MR, daytime sleepiness and napping were associated with increased risk of epilepsy, while daytime napping and frequent insomnia symptoms were linked to elevated risk of status epilepticus. <b>Conclusions</b>: Our findings reveal subtype-specific and bidirectional causal links between epilepsy and sleep-related traits. These results highlight the biological interplay between epileptic networks and sleep regulation and underscore the need for further clinical and mechanistic studies.https://www.mdpi.com/2076-3425/15/7/749epilepsystatus epilepticussleep-related traitsMendelian randomization
spellingShingle Yong-Won Shin
Sang Bin Hong
Causal Relationship Between Epilepsy, Status Epilepticus and Sleep-Related Traits: A Bidirectional Mendelian Randomization Study
Brain Sciences
epilepsy
status epilepticus
sleep-related traits
Mendelian randomization
title Causal Relationship Between Epilepsy, Status Epilepticus and Sleep-Related Traits: A Bidirectional Mendelian Randomization Study
title_full Causal Relationship Between Epilepsy, Status Epilepticus and Sleep-Related Traits: A Bidirectional Mendelian Randomization Study
title_fullStr Causal Relationship Between Epilepsy, Status Epilepticus and Sleep-Related Traits: A Bidirectional Mendelian Randomization Study
title_full_unstemmed Causal Relationship Between Epilepsy, Status Epilepticus and Sleep-Related Traits: A Bidirectional Mendelian Randomization Study
title_short Causal Relationship Between Epilepsy, Status Epilepticus and Sleep-Related Traits: A Bidirectional Mendelian Randomization Study
title_sort causal relationship between epilepsy status epilepticus and sleep related traits a bidirectional mendelian randomization study
topic epilepsy
status epilepticus
sleep-related traits
Mendelian randomization
url https://www.mdpi.com/2076-3425/15/7/749
work_keys_str_mv AT yongwonshin causalrelationshipbetweenepilepsystatusepilepticusandsleeprelatedtraitsabidirectionalmendelianrandomizationstudy
AT sangbinhong causalrelationshipbetweenepilepsystatusepilepticusandsleeprelatedtraitsabidirectionalmendelianrandomizationstudy