Li Kaiji, Li Haonan, Wang Jinchao, Chen Xin, Li Lei, Wang Cong, Zhang Shu, Zhang Jianning
Tianjin Neurological Institute, Key Laboratory of Post-Neuro injury, Neuro-repair and Regeneration in Central Nervous System, Ministry of Education and Tianjin City, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, China; Department of Neurosurgery, Tianjin Medical University General Hospital, Tianjin, China.
Department of Radiology, Tianjin Key Lab of Functional Imaging & Tianjin Institute of Radiology, Tianjin Medical University General Hospital, Tianjin, China.
Epilepsy Behav. 2025 Apr;165:110310. doi: 10.1016/j.yebeh.2025.110310. Epub 2025 Feb 24.
Observational studies have identified a strong correlation between epilepsy and sleep traits, highlighting their interactive relationship. However, no studies have specifically examined the associations between sleep traits and epilepsy. In this context, we conducted a Mendelian Randomization (MR) investigation to explore the causal nature of these associations.
We performed a two-sample Mendelian Randomization (MR) analysis model to genetically predict the causal effects of morning chronotype on epilepsy. Five MR analysis methods were conducted to analyze the final results. The inverse-variance weighted (IVW) method was used as the primary outcome. The other MR analysis methods (MR-Egger; Weighted Mode; and Weighted median (WM)) were conducted as the complement to IVW. In addition, the robustness of the MR analysis results was assessed by leave-one-out analysis.
In forward MR, epilepsy showed causal relationships with sleep duration (IVW beta = 0.008, P = 0.015). Specifically, doubling the odds of inheriting epilepsy may be associated with a 0.0075 standard deviation (SD) (95 % CI: 1.001 to 1.014) increase in sleep duration. In reverse MR, we found statistically significant associations between chronotype (evening preference) (OR = 1.397, p = 0.007) and insomnia (OR = 2.280, p = 0.025) and the risk of epilepsy.
Our two-sample Mendelian randomization analyses indicate that individuals with epilepsy frequently experience extended sleep duration. Additionally, we identified insomnia and chronotype (evening preference) as significant risk factors that increase the likelihood of developing epilepsy.
观察性研究已确定癫痫与睡眠特征之间存在密切关联,突显了它们的交互关系。然而,尚无研究专门探讨睡眠特征与癫痫之间的关联。在此背景下,我们进行了一项孟德尔随机化(MR)研究,以探究这些关联的因果性质。
我们采用两样本孟德尔随机化(MR)分析模型,从基因层面预测晨型生物钟对癫痫的因果效应。采用五种MR分析方法分析最终结果。以逆方差加权(IVW)法作为主要结果。其他MR分析方法(MR-Egger法、加权模式法和加权中位数法(WM))作为IVW法的补充。此外,通过留一法分析评估MR分析结果的稳健性。
在前瞻性MR分析中,癫痫与睡眠时间存在因果关系(IVWβ = 0.008,P = 0.015)。具体而言,癫痫遗传几率翻倍可能与睡眠时间增加0.0075标准差(SD)(95%CI:1.001至1.014)相关。在反向MR分析中,我们发现生物钟类型(偏好夜晚)(OR = 1.397,p = 0.007)和失眠(OR = 2.280,p = 0.025)与癫痫风险之间存在统计学显著关联。
我们的两样本孟德尔随机化分析表明,癫痫患者经常经历睡眠时间延长。此外,我们确定失眠和生物钟类型(偏好夜晚)是增加患癫痫可能性的重要风险因素。