Genetic evidence links alcohol, coffee, cheese, and anxiety to GERD risk: A Mendelian randomization study

In previous observational studies, an association has been found between the frequency of alcohol consumption, coffee intake, cheese consumption, and anxiety and 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 unclear. 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 were derived from a genome-wide association meta-analysis that included 78,707 cases and 288,734 European-ancestry controls. The primary analysis methods were inverse-variance weighted (IVW), weighted median, MR-Egger, simple mode, and weighted mode methods serving as complementary approaches to IVW. Sensitivity analyses were conducted using Cochran Q test, MR-Egger intercept test, and leave-one-out analysis to assess the stability of the results. The IVW results demonstrated a strong positive causal relationship between the frequency of alcohol intake (odds ratio [OR] = 1.52, 95% confidence interval [CI] = 1.25-1.84, P < .001) and anxiety (defined as having consulted a general practitioner for nerves, anxiety, tension, or depression) (OR = 22.60, 95% CI = 12.12-42.15, P < .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 < .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 > .05). This study unveils causal connections between the frequency of alcohol consumption, cheese intake, and anxiety concerning GERD. Furthermore, our analysis found no strong genetic evidence to support a causal link between coffee consumption and GERD.