Abstract
BACKGROUND: IgA nephropathy (IgAN) incidence is higher in gastroesophageal reflux disease (GERD) patients than those without. However, the causal link between them is unclear. This study aims to elucidate the causal relationship between GERD and IgAN through bidirectional Mendelian randomization (MR) analysis. METHODS: The chi-square test was employed to assess whether the incidence of IgAN was associated with GERD. Multivariate logistic regression was used to assess whether GERD is an independent risk factor for IgAN. Univariable and multivariable MR analyses were conducted to estimate the associations between GERD and IgAN. The MR analysis included inverse-variance weighted, MR-Egger, weighted median, simple mode, and weighted mode methods. Additionally, pleiotropy, heterogeneity, and sensitivity analyses were performed. RESULTS: In two independent clinical cohorts, GERD patients showed a significantly elevated risk of IgAN. After adjusting for confounding factors such as age, gender, BMI, and hypertension, the results of multivariate logistic regression indicated that GERD is a significant risk factor for IgAN. The MR analysis demonstrated that GERD significantly increased the risk of IgAN (OR = 1.378, p < 0.001). Conversely, reverse MR analysis indicated no significant increase in the risk of GERD due to IgAN. Furthermore, this study confirmed the robustness of the results, detecting no pleiotropy or heterogeneity. The multivariate MR analysis revealed that, even after adjusting for hypertension and BMI, GERD maintained a robust association with an increased risk of IgAN (OR = 1.418, p < 0.001). CONCLUSIONS: The study suggests that GERD increases the risk of IgAN. However, there is insufficient evidence to support reverse causality between the two diseases.