Causal relationship between gastroesophageal reflux disease, Barrett's esophagus, and epilepsy: A bidirectional Mendelian randomization study

Author:

Liu Xiaoduo1,Wei Tao1,Shi Lubo2,Zhou Shaojiong1,Liu Yufei1,Song Weiyi1,Que Xinwei1,Wang Zhibin1,Tang Yi13ORCID

Affiliation:

1. Department of Neurology & Innovation Center for Neurological Disorders Xuanwu Hospital, Capital Medical University, National Center for Neurological Disorders Beijing China

2. Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University National Clinical Research Center for Digestive Diseases Beijing Digestive Disease Center Beijing China

3. Neurodegenerative Laboratory of Ministry of Education of the Peoples Republic of China Beijing China

Abstract

AbstractBackgroundThe 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.MethodsWe 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.ResultsWe 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.ConclusionsUnder 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.

Funder

National Natural Science Foundation of China

National Key Research and Development Program of China

Publisher

Wiley

Subject

Behavioral Neuroscience

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