Association between Alcohol Consumption Frequency, Coffee, Cheese Intake, and Anxiety with the Risk of Gastroesophageal Reflux Disease: A Mendelian Randomization Study

Abstract

Abstract Background In previous observational research, an association has been found between the frequency of alcohol consumption, coffee intake, cheese consumption, and anxiety with the risk of gastroesophageal reflux disease (GERD). However, conflicting conclusions exist among these studies, and the causal relationship between these exposure factors and GERD remains uncertain. Methods Independent genetic variants associated with alcohol consumption frequency, coffee intake, cheese consumption, and anxiety at the genome-wide significance level were selected as instrumental variables. Summary-level data for GERD was derived from a genome-wide association meta-analysis, which included 78,707 cases and 288,734 European-ancestry controls. The primary analysis method was Inverse Variance-Weighted (IVW), with Weighted Median (WM), MR-Egger, Simple mode, and Weighted mode methods serving as complementary approaches to IVW. Sensitivity analyses were conducted using Cochran's Q test, the MR-Egger intercept test, and leave-one-out analysis to assess the stability of the results. Results The IVW results demonstrate a strong positive causal relationship between the frequency of alcohol intake (OR=1.52, 95%CI=1.25-1.84, P<0.001) and having consulted a general practitioner for nerves, anxiety, tension, or depression (OR=22.60, 95%CI=12.12-42.15, P<0.001) with GERD. A negative causal relationship was observed between genetically predicted cheese consumption and GERD (OR=0.36, 95%CI=0.26-0.50, P<0.001). However, the association between coffee consumption and GERD was not significant in the IVW analysis (OR=1.21, 95% CI, 0.98-1.60, P>0.05). Conclusions This study reveals the causal relationships between the frequency of alcohol consumption, cheese intake, and anxiety with GERD, as well as the potential role of high coffee consumption in the development of GERD.