Department of Neurology & Innovation Center for Neurological Disorders, Xuanwu Hospital, Capital Medical University, National Center for Neurological Disorders, Beijing, China.
Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University National Clinical Research Center for Digestive Diseases, Beijing Digestive Disease Center, Beijing, China.
Brain Behav. 2023 Sep;13(9):e3117. doi: 10.1002/brb3.3117. Epub 2023 Jun 8.
The incidence of gastroesophageal reflux disease (GERD) has been shown to be elevated in individuals with epilepsy. Traditional observational studies have led to a limited understanding of the effects of GERD and BE on epilepsy due to the interference of reverse causation and potential confounders.
We conducted a bidirectional two-sample Mendelian randomization (MR) analysis to determine whether GERD and BE can increase the risk of epilepsy. Genome-wide association study data on epilepsy and its subgroups were obtained from the International League Against Epilepsy consortium for primary analysis using three MR approaches and the FinnGen consortium for replication and meta-analysis. We calculated causal estimates between the two esophageal diseases and epilepsy using the inverse-variance weighted method. Sensitivity analysis was conducted to detect heterogeneity and pleiotropy.
We found a potential effect of genetically predicted GERD on the risk of epilepsy (odds ratio [OR] = 1.078; 95% confidence interval [CI], 1.014-1.146, p = .016). Specifically, GERD showed an effect on the risk of generalized epilepsy (OR = 1.163; 95% CI, 1.048-1.290, p = .004) but not focal epilepsy (OR = 1.059, 95% CI, 0.992-1.131, p = .084). Notably, BE did not show a significant causal relationship with the risks of generalized and focal epilepsy.
Under MR assumptions, our findings suggest a potential risk-increasing effect of GERD on epilepsy, especially generalized epilepsy. Considering the exploratory nature of our study, the association between GERD and epilepsy needs to be confirmed by future prospective studies.
胃食管反流病（GERD）的发病率在癫痫患者中升高。由于反向因果关系和潜在混杂因素的干扰，传统的观察性研究对 GERD 和 BE 对癫痫的影响的了解有限。
我们进行了双向两样本 Mendelian 随机化（MR）分析，以确定 GERD 和 BE 是否会增加癫痫的风险。使用三种 MR 方法从国际癫痫联盟联盟获得癫痫及其亚组的全基因组关联研究数据进行主要分析，并使用 FinnGen 联盟进行复制和荟萃分析。我们使用逆方差加权法计算两种食管疾病与癫痫之间的因果估计。进行敏感性分析以检测异质性和多效性。
我们发现遗传预测的 GERD 对癫痫风险有潜在影响（比值比 [OR] = 1.078；95%置信区间 [CI]，1.014-1.146，p =.016）。具体而言，GERD 对全面性癫痫的风险有影响（OR = 1.163；95% CI，1.048-1.290，p =.004），但对局灶性癫痫无影响（OR = 1.059，95% CI，0.992-1.131，p =.084）。值得注意的是，BE 与全面性和局灶性癫痫的风险之间没有显示出显著的因果关系。
根据 MR 假设，我们的研究结果表明 GERD 对癫痫，特别是全面性癫痫有潜在的风险增加作用。考虑到我们研究的探索性性质，GERD 和癫痫之间的关联需要通过未来的前瞻性研究来证实。
