PDF(Pubmed)
Abstract：
OBJECTIVE: The causes and triggering factors of epilepsy are still unknown. The results of genome-wide association studies can be utilized for a phenome-wide association study using Mendelian randomization (MR) to identify potential risk factors for epilepsy.
METHODS: This study utilizes two-sample MR analysis to investigate whether 316 phenotypes, including lifestyle, environmental factors, blood biomarker, and more, are causally associated with the occurrence of epilepsy. The primary analysis employed the inverse variance weighted (IVW) model, while complementary MR analysis methods (MR Egger, Wald ratio) were also employed. Sensitivity analyses were also conducted to evaluate heterogeneity and pleiotropy.
RESULTS: There was no evidence of a statistically significant causal association between the examined phenotypes and epilepsy following Bonferroni correction (p < 1.58 × 10-4) or false discovery rate correction. The results of the MR analysis indicate that the frequency of tiredness or lethargy in the last 2 weeks (p = 0.042), blood uridine (p = 0.003), blood propionylcarnitine (p = 0.041), and free cholesterol (p = 0.044) are suggestive causal risks for epilepsy. Lifestyle choices, such as sleep duration and alcohol consumption, as well as biomarkers including steroid hormone levels, hippocampal volume, and amygdala volume were not identified as causal factors for developing epilepsy (p > 0.05).
CONCLUSIONS: Our study provides additional insights into the underlying causes of epilepsy, which will serve as evidence for the prevention and control of epilepsy. The associations observed in epidemiological studies may be partially attributed to shared biological factors or lifestyle confounders.
METHODS: This study utilizes two-sample MR analysis to investigate whether 316 phenotypes, including lifestyle, environmental factors, blood biomarker, and more, are causally associated with the occurrence of epilepsy. The primary analysis employed the inverse variance weighted (IVW) model, while complementary MR analysis methods (MR Egger, Wald ratio) were also employed. Sensitivity analyses were also conducted to evaluate heterogeneity and pleiotropy.
RESULTS: There was no evidence of a statistically significant causal association between the examined phenotypes and epilepsy following Bonferroni correction (p < 1.58 × 10-4) or false discovery rate correction. The results of the MR analysis indicate that the frequency of tiredness or lethargy in the last 2 weeks (p = 0.042), blood uridine (p = 0.003), blood propionylcarnitine (p = 0.041), and free cholesterol (p = 0.044) are suggestive causal risks for epilepsy. Lifestyle choices, such as sleep duration and alcohol consumption, as well as biomarkers including steroid hormone levels, hippocampal volume, and amygdala volume were not identified as causal factors for developing epilepsy (p > 0.05).
CONCLUSIONS: Our study provides additional insights into the underlying causes of epilepsy, which will serve as evidence for the prevention and control of epilepsy. The associations observed in epidemiological studies may be partially attributed to shared biological factors or lifestyle confounders.
摘要：
目的：癫痫的病因及诱发因素尚不清楚。全基因组关联研究的结果可用于使用孟德尔随机化（MR）的全表型关联研究，以确定癫痫的潜在危险因素。
方法：本研究利用双样本MR分析来调查316种表型包括生活方式,环境因素,血液生物标志物，还有更多,与癫痫的发生有因果关系。主要分析采用逆方差加权(IVW)模型，而互补的MR分析方法(MREgger，Wald比率)也被采用。还进行了敏感性分析以评估异质性和多效性。
结果：在Bonferroni校正（p<1.58×10-4）或错误发现率校正后，没有证据表明所检查的表型与癫痫之间存在统计学上显著的因果关系。MR分析结果表明，过去2周内疲倦或嗜睡的频率（p=0.042），血尿苷（p=0.003），血丙酰肉碱（p=0.041），和游离胆固醇(p=0.044)是癫痫的提示因果风险。生活方式的选择,例如睡眠时间和饮酒，以及包括类固醇激素水平在内的生物标志物，海马体积,杏仁核体积未被确定为发生癫痫的原因因素(p>0.05)。
结论：我们的研究为癫痫的潜在原因提供了更多的见解，这将作为预防和控制癫痫的证据。在流行病学研究中观察到的关联可能部分归因于共同的生物因素或生活方式混杂因素。
方法：本研究利用双样本MR分析来调查316种表型包括生活方式,环境因素,血液生物标志物，还有更多,与癫痫的发生有因果关系。主要分析采用逆方差加权(IVW)模型，而互补的MR分析方法(MREgger，Wald比率)也被采用。还进行了敏感性分析以评估异质性和多效性。
结果：在Bonferroni校正（p<1.58×10-4）或错误发现率校正后，没有证据表明所检查的表型与癫痫之间存在统计学上显著的因果关系。MR分析结果表明，过去2周内疲倦或嗜睡的频率（p=0.042），血尿苷（p=0.003），血丙酰肉碱（p=0.041），和游离胆固醇(p=0.044)是癫痫的提示因果风险。生活方式的选择,例如睡眠时间和饮酒，以及包括类固醇激素水平在内的生物标志物，海马体积,杏仁核体积未被确定为发生癫痫的原因因素(p>0.05)。
结论：我们的研究为癫痫的潜在原因提供了更多的见解，这将作为预防和控制癫痫的证据。在流行病学研究中观察到的关联可能部分归因于共同的生物因素或生活方式混杂因素。
