胃食管反流病和急性胰腺炎的因果关联：孟德尔随机化研究

Causal Association between Gastroesophageal Reflux Disease and Acute Pancreatitis: A Mendelian Randomization Study

摘要: 目的：本研究采用了两样本孟德尔随机化(MR)方法系统地探讨了GERD与AP之间的潜在因果关系。方法：采用逆方差加权(IVW)方法，我们得出了因果推断。为了提高结果的稳健性，我们使用了一系列方法，包括孟德尔随机化多效性残差和异常值(MR-PRESSO)、简单模式、加权模式、加权中位数估计器(WME)和MR-Egger回归。结果：我们的分析确定了80个遗传变异，这些变异能够强烈预测GERD的发病，满足严格的标准(p值 < 5 × 10⁻⁸)并显示出独立性(r² < 0.01)。从IVW模型得出的因果效应估计表明，GERD与增加的AP风险之间存在统计学上显著的关联(95% CI = 1.402~2.029, OR = 1.6870, p = 2.940 × 10⁻⁸)。结论：总之，我们的MR探索提供了强有力的证据，支持GERD与AP之间存在因果关系，以及GERD和AP的多学科个体化治疗。

Abstract: Objective: This study systematically delves into the potential causal correlation between GERD and AP, employing the two-sample Mendelian randomization (MR) methodology. Methods: Employing the Inverse Variance Weighted (IVW) approach, we derived causal inferences. A suite of methodologies, including Mendelian Randomization Pleiotropy Residual Sum and Outlier (MR-PRESSO), Simple Mode, Weighted Mode, Weighted Median Estimator (WME), and MR-Egger regression, was utilized to increase the robustness of the results. Results: Our analysis identified 80 genetic variants robustly anticipating GERD onset, meeting stringent criteria (p-value < 5 × 10⁻⁸) and demonstrating independence (r² < 0.01). Causal-effect estimates derived from the IVW model indicate a statistically significant association, demonstrating GERD’s marked link to an augmented AP risk (95% CI = 1.402~2.029, OR = 1.6870, p = 2.940 × 10⁻⁸). Conclusion: In summation, our MR exploration yields robust evidence supporting the presence of a causal relationship between GERD and AP, as well as for multidisciplinary individualized treatment of GERD and AP.