He Zhipeng, Tang Shishi, Hu Yurong, Li Yuxuan, Liang Junhao, Fang Li, Li Miaoxin, Chen Ziyi, Zhou Yi
Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, Guangdong, China.
School of Computer Science, China University of Geosciences, Wuhan, Hubei, China.
Health Data Sci. 2025 Aug 5;5:0283. doi: 10.34133/hds.0283. eCollection 2025.
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. Genetic instruments were obtained from the latest genome-wide association studies (GWAS) of 69,995 individuals ( = 27,559, = 42,436) issued by the International League Against Epilepsy. The GWAS summary SC/FC data within RSNs ( = 23,985, = 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. 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. 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.
在癫痫的观察性研究中，静息态网络（RSNs）内的脑连接改变已被广泛报道。然而，癫痫与RSNs内结构连接（SC）/功能连接（FC）之间的因果关系仍不清楚。我们进行了双向双样本孟德尔随机化（MR），以探索癫痫亚型与RSNs内脑连接特性之间的因果关系。遗传工具来自国际抗癫痫联盟发布的针对69995名个体（病例组 = 27559，对照组 = 42436）的最新全基因组关联研究（GWAS）。RSNs内的GWAS汇总SC/FC数据（病例组 = 23985，对照组 = 24336）来自神经基因组学和认知研究中心。我们通过双向双样本MR分析研究癫痫亚型与RSNs内脑连接之间的因果关系。我们发现，全身性遗传性癫痫风险的增加与对背侧注意力和躯体运动FC的因果效应一致。在反向MR分析中，FC/SC连接对癫痫亚型没有提示性的因果效应。这项研究揭示了RSNs内FC/SC水平与癫痫及其亚型之间的关联。这一见解可能会在脑结构和功能网络层面为不同亚型的癫痫产生关键的干预策略。
