Department of Radiology, Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China.
Brain Behav. 2024 Oct;14(10):e70051. doi: 10.1002/brb3.70051.
Epilepsy, a complex neurological disorder, is closely linked with structural and functional irregularities in the brain. However, the causal relationship between brain imaging-derived phenotypes (IDPs) and epilepsy remains unclear. This study aimed to investigate this relationship by employing a two-sample bidirectional Mendelian randomization (MR) approach.
The analysis involved 3935 cerebral IDPs from the UK Biobank and all documented cases of epilepsy (all epilepsies) cohorts from the International League Against Epilepsy, with further validation through replication and meta-analyses using epilepsy Genome-Wide Association Studies datasets from the FinnGen database. Additionally, a multivariate MR analysis framework was utilized to assess the direct impact of IDPs on all epilepsies. Furthermore, we performed a bidirectional MR analysis to investigate the relationship between the IDPs identified in all epilepsies and the 15 specific subtypes of epilepsy.
The study identified significant causal links between four IDPs and epilepsy risk. Decreased fractional anisotropy in the left inferior longitudinal fasciculus was associated with a higher risk of epilepsy (odds ratio [OR]: 0.89, p = 3.31×10). Conversely, increased mean L1 in the left posterior thalamic radiation (PTR) was independently associated with a heightened epilepsy risk (OR: 1.14, p = 4.72×10). Elevated L3 in the left cingulate gyrus was also linked to an increased risk (OR: 1.09, p = .03), while decreased intracellular volume fraction in the corpus callosum was correlated with higher epilepsy risk (OR: 0.94, p = 1.15×10). Subtype analysis revealed that three of these IDPs are primarily associated with focal epilepsy (FE). Notably, increased L1 in the left PTR was linked to an elevated risk of hippocampal sclerosis (HS) and lesion-negative FE, whereas elevated L3 in the left cingulate gyrus was associated with HS-related FE.
Our research offers genetic evidence for a causal link between brain IDPs and epilepsy. These results enhance our understanding of the structural brain changes associated with the onset and progression of epilepsy.
癫痫是一种复杂的神经疾病，与大脑的结构和功能异常密切相关。然而，脑影像衍生表型（IDPs）与癫痫之间的因果关系尚不清楚。本研究采用两样本双向孟德尔随机化（MR）方法来研究这种关系。
分析中纳入了来自英国生物库的 3935 项大脑 IDPs 和国际抗癫痫联盟（ILAE）所有记录的癫痫病例（所有癫痫）队列，使用 FinnGen 数据库中的癫痫全基因组关联研究数据集进行了复制和荟萃分析验证。此外，还使用多变量 MR 分析框架评估了 IDPs 对所有癫痫的直接影响。进一步进行双向 MR 分析，以研究所有癫痫中识别的 IDPs 与 15 种特定癫痫亚型之间的关系。
研究发现四个 IDPs 与癫痫风险之间存在显著的因果关系。左侧下纵束的分数各向异性降低与癫痫风险增加相关（比值比 [OR]：0.89，p = 3.31×10）。相反，左侧后丘脑辐射（PTR）的平均 L1 增加与癫痫风险升高独立相关（OR：1.14，p = 4.72×10）。左侧扣带回的 L3 升高也与风险增加相关（OR：1.09，p = 0.03），而胼胝体的细胞内体积分数降低与癫痫风险增加相关（OR：0.94，p = 1.15×10）。亚型分析表明，这四个 IDPs 中的三个主要与局灶性癫痫（FE）相关。值得注意的是，左侧 PTR 的 L1 增加与海马硬化（HS）和无病变 FE 的风险升高相关，而左侧扣带回的 L3 升高与 HS 相关的 FE 相关。
本研究提供了遗传证据，证明脑 IDPs 与癫痫之间存在因果关系。这些结果增强了我们对与癫痫发作和进展相关的结构性脑变化的理解。
