Causal association between gastroesophageal reflux disease and anemia: Mendelian randomization analysis

Background Previous observational studies have indicated a possible link between gastroesophageal reflux disease (GERD) and anemia, but the causal relationships and specific anemia subtypes involved remain unclear. Methods To explore the causal relationship between GERD and anemia risk, we conducted a two-sample Mendelian randomization study using the inverse-variance weighting (IVW) analytical method. After stringent selection, 75 and 76 independent single nucleotide polymorphisms were used as instrumental variables for GERD in analyses of anemia and iron-deficiency anemia (IDA), respectively. Results IVW analysis demonstrated that genetically predicted GERD was associated with elevated anemia odds ratios (OR) = 1.35; 95% confidence interval (CI): 1.17-1.56, P < 0.001 or IDA risk (OR = 1.30; 95% CI: 1.18-1.42; P < 0.001). The results of the weighted median analysis were also consistent with those of the IVW analysis and provided evidence of causal links ( P < 0.05). However, the sensitivity analyses revealed no evidence of horizontal pleiotropy or heterogeneity. Conclusions Our study provides evidence consistent with a causal relationship between GERD and an elevated risk of developing anemia or IDA. However, because all GWAS datasets used in this study were derived from individuals of European ancestry, the generalizability of our findings to other populations remains uncertain and requires confirmation in diverse ethnic groups.