Exploring the causality between educational attainment and gastroesophageal reflux disease: A Mendelian randomization study

Abstract

Background and objectives: Observational studies suggest that higher educational attainment (EA) contributes to the prevention and treatment of gastroesophageal reflux disease (GERD). However, the causality of this relationship is not supported by strong evidence. We used publicly available genetic summary data, including that on EA, GERD, and the common risk of GERD, to prove this causality.

Methods: Multiple methods in Mendelian randomization (MR) were employed to evaluate the causality. The leave-one-out sensitivity test, MR-Egger regression, and multivariable MR (MVMR) analysis were applied to evaluate the MR results.

Results: Higher EA was significantly associated with lower GERD risk (inverse variance weighted method, odds ratio [OR]: 0.979, 95% confidence interval [CI]: 0.975-0.984, P <0.001). Similar results were obtained when the weighted median and weighted mode were used for causal estimation. After adjusting for potential mediators, the MVMR analysis showed that body mass index (BMI) and EA were still significantly correlated and negatively correlated with GERD (OR: 0.997, 95% CI: 0.996-0.998, P =0.008 and OR: 0.981, 95% CI: 0.977-0.984, P <0.001), respectively.

Conclusions: Higher levels of EA may have a protective effect against GERD by having a negative causal relationship. Additionally, BMI may be a crucial factor in the EA-GERD pathway.

Keywords: Causality; Educational attainment; Gastroesophageal reflux disease; Genome-wide association studies; Mendelian randomization.