Brain Connectivity Yields Insights into the Pathogenesis of Epilepsy and Subtypes: Evidence from Mendelian Randomization Analysis

Background: Alterations of brain connectivity within resting-state networks (RSNs) have been widely reported in observational studies on epilepsy. However, the causal relationship between epilepsy and structural connectivity (SC)/functional connectivity (FC) within RSNs remain unclear. We conducted...

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Main Authors: Zhipeng He, Shishi Tang, Yurong Hu, Yuxuan Li, Junhao Liang, Li Fang, Miaoxin Li, Ziyi Chen, Yi Zhou
Format: Article
Language:English
Published: American Association for the Advancement of Science (AAAS) 2025-01-01
Series:Health Data Science
Online Access:https://spj.science.org/doi/10.34133/hds.0283
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author Zhipeng He
Shishi Tang
Yurong Hu
Yuxuan Li
Junhao Liang
Li Fang
Miaoxin Li
Ziyi Chen
Yi Zhou
author_facet Zhipeng He
Shishi Tang
Yurong Hu
Yuxuan Li
Junhao Liang
Li Fang
Miaoxin Li
Ziyi Chen
Yi Zhou
author_sort Zhipeng He
collection DOAJ
description Background: Alterations of brain connectivity within resting-state networks (RSNs) have been widely reported in observational studies on epilepsy. However, the causal relationship between epilepsy and structural connectivity (SC)/functional connectivity (FC) within RSNs remain unclear. We conducted a bidirectional two-sample Mendelian randomization (MR) to explore the causal relationship between epilepsy subtypes and brain connectivity properties within RSNs. Methods: Genetic instruments were obtained from the latest genome-wide association studies (GWAS) of 69,995 individuals (Ncases = 27,559, Ncontrols = 42,436) issued by the International League Against Epilepsy. The GWAS summary SC/FC data within RSNs (NSC = 23,985, NFC = 24,336) were sourced from the Center for Neurogenomics and Cognitive Research. We investigate the causal relationship between epilepsy subtypes and brain connectivity within RSNs through a bidirectional two-sample MR analysis. Results: We found that the increased risk of generalized genetic epilepsy is consistent with a causal effect on dorsal attention and somatomotor FC. In the reverse MR analysis, there was no suggestive causal effect of FC/SC connectivity on epilepsy subtypes. Conclusions: This study shed light on the associations of FC/SC levels within the RSNs and epilepsy along with its subtypes. This insight could yield crucial intervention strategies to different subtypes of epilepsy at the level of brain structure and functional networks.
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publishDate 2025-01-01
publisher American Association for the Advancement of Science (AAAS)
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spelling doaj-art-26a27c3ebb984a72af8bacf82fdae10d2025-08-20T04:02:12ZengAmerican Association for the Advancement of Science (AAAS)Health Data Science2765-87832025-01-01510.34133/hds.0283Brain Connectivity Yields Insights into the Pathogenesis of Epilepsy and Subtypes: Evidence from Mendelian Randomization AnalysisZhipeng He0Shishi Tang1Yurong Hu2Yuxuan Li3Junhao Liang4Li Fang5Miaoxin Li6Ziyi Chen7Yi Zhou8Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.School of Computer Science, China University of Geosciences, Wuhan, Hubei, China.Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China.Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.Background: Alterations of brain connectivity within resting-state networks (RSNs) have been widely reported in observational studies on epilepsy. However, the causal relationship between epilepsy and structural connectivity (SC)/functional connectivity (FC) within RSNs remain unclear. We conducted a bidirectional two-sample Mendelian randomization (MR) to explore the causal relationship between epilepsy subtypes and brain connectivity properties within RSNs. Methods: Genetic instruments were obtained from the latest genome-wide association studies (GWAS) of 69,995 individuals (Ncases = 27,559, Ncontrols = 42,436) issued by the International League Against Epilepsy. The GWAS summary SC/FC data within RSNs (NSC = 23,985, NFC = 24,336) were sourced from the Center for Neurogenomics and Cognitive Research. We investigate the causal relationship between epilepsy subtypes and brain connectivity within RSNs through a bidirectional two-sample MR analysis. Results: We found that the increased risk of generalized genetic epilepsy is consistent with a causal effect on dorsal attention and somatomotor FC. In the reverse MR analysis, there was no suggestive causal effect of FC/SC connectivity on epilepsy subtypes. Conclusions: This study shed light on the associations of FC/SC levels within the RSNs and epilepsy along with its subtypes. This insight could yield crucial intervention strategies to different subtypes of epilepsy at the level of brain structure and functional networks.https://spj.science.org/doi/10.34133/hds.0283
spellingShingle Zhipeng He
Shishi Tang
Yurong Hu
Yuxuan Li
Junhao Liang
Li Fang
Miaoxin Li
Ziyi Chen
Yi Zhou
Brain Connectivity Yields Insights into the Pathogenesis of Epilepsy and Subtypes: Evidence from Mendelian Randomization Analysis
Health Data Science
title Brain Connectivity Yields Insights into the Pathogenesis of Epilepsy and Subtypes: Evidence from Mendelian Randomization Analysis
title_full Brain Connectivity Yields Insights into the Pathogenesis of Epilepsy and Subtypes: Evidence from Mendelian Randomization Analysis
title_fullStr Brain Connectivity Yields Insights into the Pathogenesis of Epilepsy and Subtypes: Evidence from Mendelian Randomization Analysis
title_full_unstemmed Brain Connectivity Yields Insights into the Pathogenesis of Epilepsy and Subtypes: Evidence from Mendelian Randomization Analysis
title_short Brain Connectivity Yields Insights into the Pathogenesis of Epilepsy and Subtypes: Evidence from Mendelian Randomization Analysis
title_sort brain connectivity yields insights into the pathogenesis of epilepsy and subtypes evidence from mendelian randomization analysis
url https://spj.science.org/doi/10.34133/hds.0283
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