Exploring the causal relationship between serum EFNB2 levels and epilepsy: a bidirectional Mendelian randomization and co-localization analysis

Abstract Background Epilepsy is a severe neurological disorder characterized by persistent seizures and, in some patients, associated neurobiological, cognitive, and psychosocial consequences. It is influenced by various genetic factors, including the Ephrin-B2 (EFNB2) gene. Methods This study utili...

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Main Authors: Xudong Zhang, Yuhao Xu, Zehan Wu, Xiang Zou
Format: Article
Language:English
Published: BMC 2025-03-01
Series:BMC Neurology
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Online Access:https://doi.org/10.1186/s12883-025-04115-6
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author Xudong Zhang
Yuhao Xu
Zehan Wu
Xiang Zou
author_facet Xudong Zhang
Yuhao Xu
Zehan Wu
Xiang Zou
author_sort Xudong Zhang
collection DOAJ
description Abstract Background Epilepsy is a severe neurological disorder characterized by persistent seizures and, in some patients, associated neurobiological, cognitive, and psychosocial consequences. It is influenced by various genetic factors, including the Ephrin-B2 (EFNB2) gene. Methods This study utilized bidirectional Mendelian randomization (MR) to explore the potential causal relationship between serum levels of EFNB2 and epilepsy using data from extensive genome-wide association studies (GWAS). We selected serum levels of EFNB2 and generalized epilepsy traits, applying strict criteria for instrumental variables to ensure validity and mitigate confounding influences. The analysis included sensitivity tests like the MR pleiotropy residuals and outliers test, as well as co-localization to evaluate shared genetic influences. Results Our results indicated a significant causal relationship between serum levels of EFNB2 and epilepsy, suggesting that EFNB2 could be involved in the pathogenesis of epilepsy through mechanisms that may not be directly linked to shared genetic pathways. Conclusion These results suggest a potential association between EFNB2 and epilepsy, highlighting the need for further studies to clarify its role and explore its possible relevance as a therapeutic target.
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spelling doaj-art-fa44e71e7e834778a483dd6459c67feb2025-08-20T03:05:52ZengBMCBMC Neurology1471-23772025-03-0125111110.1186/s12883-025-04115-6Exploring the causal relationship between serum EFNB2 levels and epilepsy: a bidirectional Mendelian randomization and co-localization analysisXudong Zhang0Yuhao Xu1Zehan Wu2Xiang Zou3Department of Neurosurgery, Huashan Hospital, Fudan UniversityDepartment of Neurosurgery, Huashan Hospital, Fudan UniversityDepartment of Neurosurgery, Huashan Hospital, Fudan UniversityDepartment of Neurosurgery, Huashan Hospital, Fudan UniversityAbstract Background Epilepsy is a severe neurological disorder characterized by persistent seizures and, in some patients, associated neurobiological, cognitive, and psychosocial consequences. It is influenced by various genetic factors, including the Ephrin-B2 (EFNB2) gene. Methods This study utilized bidirectional Mendelian randomization (MR) to explore the potential causal relationship between serum levels of EFNB2 and epilepsy using data from extensive genome-wide association studies (GWAS). We selected serum levels of EFNB2 and generalized epilepsy traits, applying strict criteria for instrumental variables to ensure validity and mitigate confounding influences. The analysis included sensitivity tests like the MR pleiotropy residuals and outliers test, as well as co-localization to evaluate shared genetic influences. Results Our results indicated a significant causal relationship between serum levels of EFNB2 and epilepsy, suggesting that EFNB2 could be involved in the pathogenesis of epilepsy through mechanisms that may not be directly linked to shared genetic pathways. Conclusion These results suggest a potential association between EFNB2 and epilepsy, highlighting the need for further studies to clarify its role and explore its possible relevance as a therapeutic target.https://doi.org/10.1186/s12883-025-04115-6EpilepsyEFNB2Mendelian randomizationmTORMAPK/ERKSynaptic remodeling
spellingShingle Xudong Zhang
Yuhao Xu
Zehan Wu
Xiang Zou
Exploring the causal relationship between serum EFNB2 levels and epilepsy: a bidirectional Mendelian randomization and co-localization analysis
BMC Neurology
Epilepsy
EFNB2
Mendelian randomization
mTOR
MAPK/ERK
Synaptic remodeling
title Exploring the causal relationship between serum EFNB2 levels and epilepsy: a bidirectional Mendelian randomization and co-localization analysis
title_full Exploring the causal relationship between serum EFNB2 levels and epilepsy: a bidirectional Mendelian randomization and co-localization analysis
title_fullStr Exploring the causal relationship between serum EFNB2 levels and epilepsy: a bidirectional Mendelian randomization and co-localization analysis
title_full_unstemmed Exploring the causal relationship between serum EFNB2 levels and epilepsy: a bidirectional Mendelian randomization and co-localization analysis
title_short Exploring the causal relationship between serum EFNB2 levels and epilepsy: a bidirectional Mendelian randomization and co-localization analysis
title_sort exploring the causal relationship between serum efnb2 levels and epilepsy a bidirectional mendelian randomization and co localization analysis
topic Epilepsy
EFNB2
Mendelian randomization
mTOR
MAPK/ERK
Synaptic remodeling
url https://doi.org/10.1186/s12883-025-04115-6
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AT zehanwu exploringthecausalrelationshipbetweenserumefnb2levelsandepilepsyabidirectionalmendelianrandomizationandcolocalizationanalysis
AT xiangzou exploringthecausalrelationshipbetweenserumefnb2levelsandepilepsyabidirectionalmendelianrandomizationandcolocalizationanalysis