Causal relationship between gastroesophageal reflux disease, Barrett's esophagus, and epilepsy: A bidirectional Mendelian randomization study.
Causal relationship between gastroesophageal reflux disease, Barrett's esophagus, and epilepsy: A bidirectional Mendelian randomization study.
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DOI：
10.1002/brb3.3117
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发表时间：
2023-09
影响因子：
3.1
通讯作者：
Tang, Yi
中科院分区：
文献类型：
--
作者：
Liu, Xiaoduo;Wei, Tao;Shi, Lubo;Zhou, Shaojiong;Liu, Yufei;Song, Weiyi;Que, Xinwei;Wang, Zhibin;Tang, Yi
胃食管反流病（GERD）的发病率已被证明是在癫痫患者中升高。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对癫痫的影响了解有限。我们进行了双向双样本孟德尔随机化（MR）分析，以确定GERD和BE是否会增加癫痫的风险。癫痫及其亚组的全基因组关联研究数据来自国际抗癫痫联盟联盟（International League Against Epilepsy consortium），用于使用三种MR方法进行初步分析，并来自FinnGen联盟（FinnGen consortium）进行复制和Meta分析。我们使用逆方差加权法计算了两种食管疾病和癫痫之间的因果关系估计。进行敏感性分析以检测异质性和多效性。我们发现基因预测GERD对癫痫风险的潜在影响（比值比[OR] = 1.078; 95%置信区间[CI]，1.014-1.146，p = 0.016）。具体而言，GERD对全身性癫痫风险有影响（OR = 1.163; 95% CI，1.048-1.290，p = .004），但对局灶性癫痫风险无影响（OR = 1.059，95% CI，0.992-1.131，p = .084）。值得注意的是，BE与全身性和局灶性癫痫的风险没有显着的因果关系。在MR假设下，我们的研究结果表明GERD对癫痫，特别是全身性癫痫有潜在的风险增加作用。考虑到我们研究的探索性，GERD和癫痫之间的关联需要通过未来的前瞻性研究来证实。遗传预测GERD导致癫痫的潜在风险增加，特别是全身性癫痫。遗传预测BE和癫痫被发现没有因果关系。神经刺激可能是介导GERD导致癫痫的一种可能机制。
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. Genetically predicted GERD leads to a potential increased risk of epilepsy, especially generalized epilepsy. Genetically predicted BE and epilepsy are found to have no causal relationship. Neurostimulation may be a possible mechanism that mediates GERD leading to epilepsy.
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影响因子：
1.4
作者：
Finsterer J
通讯作者：
Finsterer J
影响因子：
2.1
作者：
Bowden J;Davey Smith G;Haycock PC;Burgess S
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Burgess S
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作者：
AlNamshan, Mohammed K.;AlKharashi, Nawaf M.;AlSaif, Shahad A.
通讯作者：
AlSaif, Shahad A.
影响因子：
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作者：
Harrington, JW;Brand, DA;Edwards, KS
通讯作者：
Edwards, KS
影响因子：
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作者：
Jacoby, Peter;Wong, Kingsley;Downs, Jenny
通讯作者：
Downs, Jenny