Causal Relationships Between Gastroesophageal Reflux Disease and Myocardial Infarction: Insights From Univariable and Multivariable Mendelian Randomization Analyses.
Xiaoya Zheng, Teng Hu, Tianxiang Fang, Pengpeng Su, Yingsong Wang, Ning Huangfu
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引用次数: 0
Abstract
Background: Observational studies have indicated that gastroesophageal reflux disease (GERD) is connected to myocardial infarction (MI). Nonetheless, the question of causality in these relationships remains unresolved, given the potential influence of confounding variables. The aim is to study the causal link of GERD with MI and determine whether MI factors have any mediation effects in the causative chain.
Methods: GERD (129,080 cases and 473,524 controls) and MI (831,000 individuals) were obtained from the latest genome-wide association study summary-level data. Two-sample Mendelian randomization (MR) analyses were performed to assess the associations of genetically predicted GERD with MI risk. After adjusting for several confounders, multivariable MR was employed to determine the independent impacts of GERD on MI risk. Two-step MR analyses were carried out to investigate the mediating impacts of these modifiable factors in the relationships between GERD and MI.
Results: The current univariable MR analysis indicated that GERD was connected to MI (odds ratio [OR] = 1.61; 95% confidence interval [CI]: 1.48-1.76; p = 1.01 × 10-26), whereas this correlation remained after controlling for body mass index, cigarettes per day, and alcohol consumption. Two-step MR found that several MI-associated risk factors mediated the associations between GERD and MI, with hypertension (mediation proportion: 14.4%) and type-2 diabetes mellitus (12.0%) exhibiting higher mediation proportions among the mediating networks.
Conclusion: This study identifies modifiable cardiovascular risk factors that may mediate the GERD-MI association, with hypertension (14.4%) and T2DM (12.0%) identified as the predominant modifiable mediators. These findings highlight the clinical importance of integrated cardiometabolic monitoring in GERD patients, suggesting that targeted management of blood pressure and glycemic control may mitigate MI risk in GERD populations.
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Annals of Human Genetics publishes material directly concerned with human genetics or the application of scientific principles and techniques to any aspect of human inheritance. Papers that describe work on other species that may be relevant to human genetics will also be considered. Mathematical models should include examples of application to data where possible.
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