Brain imaging traits and epilepsy: Unraveling causal links via mendelian randomization

IF 2.6 3区 心理学 Q2 BEHAVIORAL SCIENCES Brain and Behavior Pub Date : 2024-09-30 DOI:10.1002/brb3.70051
Fangyan Li, Maowen Tang, Cheng Hao, Menghua Yang, Yue Pan, Pinggui Lei
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Abstract

Background

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.

Methods

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.

Results

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 = 3.31×10−5). Conversely, increased mean L1 in the left posterior thalamic radiation (PTR) was independently associated with a heightened epilepsy risk (OR: 1.14, p = 4.72×10−5). 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 = 1.15×10−4). 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.

Conclusions

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.

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大脑成像特征与癫痫:通过 "泯灭随机化 "揭示因果联系。
背景:癫痫是一种复杂的神经系统疾病,与大脑结构和功能异常密切相关。然而,脑成像衍生表型(IDPs)与癫痫之间的因果关系仍不清楚。本研究旨在通过双样本双向孟德尔随机化(MR)方法研究这种关系:分析涉及英国生物库(UK Biobank)的3935例脑IDP和国际抗癫痫联盟(International League Against Epilepsy)的所有记录在案的癫痫病例(所有癫痫)队列,并通过使用FinnGen数据库的癫痫全基因组关联研究数据集进行复制和荟萃分析进一步验证。此外,我们还利用多变量 MR 分析框架来评估 IDPs 对所有癫痫的直接影响。此外,我们还进行了双向磁共振分析,研究在所有癫痫中发现的IDPs与15种特定癫痫亚型之间的关系:研究发现了四种 IDP 与癫痫风险之间的重要因果关系。左下纵筋束分数各向异性降低与癫痫风险较高有关(几率比 [OR]:0.89,P = 3.31×10-5)。相反,左丘脑后辐射(PTR)平均 L1 的增加与癫痫风险的增加有独立关联(OR:1.14,p = 4.72×10-5)。左侧扣带回的 L3 升高也与风险增加有关(OR:1.09,p = .03),而胼胝体的细胞内体积分数降低与癫痫风险增加有关(OR:0.94,p = 1.15×10-4)。亚型分析表明,其中三种 IDP 主要与局灶性癫痫(FE)有关。值得注意的是,左侧PTR的L1增高与海马硬化(HS)和病变阴性FE的风险升高有关,而左侧扣带回的L3增高与HS相关的FE有关:我们的研究为大脑 IDPs 与癫痫之间的因果关系提供了遗传学证据。这些结果加深了我们对与癫痫发病和进展相关的大脑结构变化的理解。
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来源期刊
Brain and Behavior
Brain and Behavior BEHAVIORAL SCIENCES-NEUROSCIENCES
CiteScore
5.30
自引率
0.00%
发文量
352
审稿时长
14 weeks
期刊介绍: Brain and Behavior is supported by other journals published by Wiley, including a number of society-owned journals. The journals listed below support Brain and Behavior and participate in the Manuscript Transfer Program by referring articles of suitable quality and offering authors the option to have their paper, with any peer review reports, automatically transferred to Brain and Behavior. * [Acta Psychiatrica Scandinavica](https://publons.com/journal/1366/acta-psychiatrica-scandinavica) * [Addiction Biology](https://publons.com/journal/1523/addiction-biology) * [Aggressive Behavior](https://publons.com/journal/3611/aggressive-behavior) * [Brain Pathology](https://publons.com/journal/1787/brain-pathology) * [Child: Care, Health and Development](https://publons.com/journal/6111/child-care-health-and-development) * [Criminal Behaviour and Mental Health](https://publons.com/journal/3839/criminal-behaviour-and-mental-health) * [Depression and Anxiety](https://publons.com/journal/1528/depression-and-anxiety) * Developmental Neurobiology * [Developmental Science](https://publons.com/journal/1069/developmental-science) * [European Journal of Neuroscience](https://publons.com/journal/1441/european-journal-of-neuroscience) * [Genes, Brain and Behavior](https://publons.com/journal/1635/genes-brain-and-behavior) * [GLIA](https://publons.com/journal/1287/glia) * [Hippocampus](https://publons.com/journal/1056/hippocampus) * [Human Brain Mapping](https://publons.com/journal/500/human-brain-mapping) * [Journal for the Theory of Social Behaviour](https://publons.com/journal/7330/journal-for-the-theory-of-social-behaviour) * [Journal of Comparative Neurology](https://publons.com/journal/1306/journal-of-comparative-neurology) * [Journal of Neuroimaging](https://publons.com/journal/6379/journal-of-neuroimaging) * [Journal of Neuroscience Research](https://publons.com/journal/2778/journal-of-neuroscience-research) * [Journal of Organizational Behavior](https://publons.com/journal/1123/journal-of-organizational-behavior) * [Journal of the Peripheral Nervous System](https://publons.com/journal/3929/journal-of-the-peripheral-nervous-system) * [Muscle & Nerve](https://publons.com/journal/4448/muscle-and-nerve) * [Neural Pathology and Applied Neurobiology](https://publons.com/journal/2401/neuropathology-and-applied-neurobiology)
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