Background In observational studies, dietary intakes are associated with gastroesophageal reflux disease (GERD). Aim: To conduct a two-sample mendelian randomization (MR) analysis to determine whether those associations are causal. Methods To explore the relationship between dietary intake and the risk of GERD, we extracted appropriate single nucleotide polymorphisms from genome-wide association study data on 24 dietary intakes. Three methods were adopted for data analysis: Inverse variance weighting, weighted median methods, and MR-Egger's method. The odds ratio (OR) and 95% confidence interval (CI) were used to evaluate the causal association between dietary intake and GERD. Results Our univariate Mendelian randomization (UVMR) results showed significant evidence that pork intake (OR, 2.83; 95%CI: 1.76-4.55; P = 1.84 x 10(-5)), beer intake (OR, 2.70, 95%CI: 2.00-3.64; P = 6.54 x 10(-11)), non-oily fish intake (OR, 2.41; 95%CI: 1.49-3.91; P = 3.59 x 10(-4)) have a protective effect on GERD. In addition, dried fruit intake (OR, 0.37; 95%CI: 0.27-0.50; 6.27 x 10(-11)), red wine intake (OR, 0.34; 95%CI: 0.25-0.47; P = 1.90 x 10(-11)), cheese intake (OR, 0.46; 95%CI: 0.39-0.55; P =3.73 x 10(-19)), bread intake (OR, 0.72; 95%CI: 0.56-0.92; P = 0.0009) and cereal intake (OR, 0.45; 95%CI: 0.36-0.57; P = 2.07 x 10(-11)) were negatively associated with the risk of GERD. There was a suggestive association for genetically predicted coffee intake (OR per one SD increase, 1.22, 95%CI: 1.03-1.44; P = 0.019). Multivariate Mendelian randomization further confirmed that dried fruit intake, red wine intake, cheese intake, and cereal intake directly affected GERD. In contrast, the impact of pork intake, beer intake, non-oily fish intake, and bread intake on GERD was partly driven by the common risk factors for GERD. However, after adjusting for all four elements, there was no longer a suggestive association between coffee intake and GERD. Conclusion This study provides MR evidence to support the causal relationship between a broad range of dietary intake and GERD, providing new insights for the treatment and prevention of GERD.
