The American journal of the medical sciences · 2026
Causal associations between gastroesophageal reflux disease and gastroduodenal ulcer: A two-sample mendelian randomisation study.
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Jiang Mingming, Fang Weiwei, Hua Xie
Аннотация
INTRODUCTION: Both common diseases are gastroesophageal reflux disease (GERD) and gastroduodenal ulcer. However, whether GERD causes gastroduodenal ulcers remains uncertain or if the reverse relationship exists. Using Mendelian randomisation, we investigated the potential causal link between GERD and gastroduodenal ulcers.
METHODS: We conducted genome-wide genetic analyses based on extensive datasets: the European population GERD dataset (with 2320,781 SNPs) and the gastroduodenal ulcer dataset (with 16,380,400 SNPs). We used the R language to perform five MR Analyses, including inverse variance weighting, MR-Egger regression, weighted median, weighted model, and simple model, to speculate on the potential causal relationship between GERD and gastroduodenal ulcer. Additionally, sensitivity analysis, heterogeneity, and horizontal pleiotropy tests were performed to assess the robustness of the MR results.
RESULTS: Our study suggest a possible causal relationship between GERD and an increased risk of gastroduodenal ulcer (GU, IVW method, OR = 1.01) (95% CI: 1.00 - 1.01, P = 0.025). The weighted median method produced a similar estimate (OR = 1.01) (95% CI: 1.00 - 1.02; P = 0.019), whereas MR-Egger showed no significant association. No evidence of horizontal pleiotropy was observed. The reverse MR analysis indicated that GU did not have a causal influence on GERD.7 CONCLUSIONS: Our two-sample MR analysis supports the notion that GERD elevates the risk of gastroduodenal ulcers. However, further investigation is needed to elucidate the underlying mechanisms.
METHODS: We conducted genome-wide genetic analyses based on extensive datasets: the European population GERD dataset (with 2320,781 SNPs) and the gastroduodenal ulcer dataset (with 16,380,400 SNPs). We used the R language to perform five MR Analyses, including inverse variance weighting, MR-Egger regression, weighted median, weighted model, and simple model, to speculate on the potential causal relationship between GERD and gastroduodenal ulcer. Additionally, sensitivity analysis, heterogeneity, and horizontal pleiotropy tests were performed to assess the robustness of the MR results.
RESULTS: Our study suggest a possible causal relationship between GERD and an increased risk of gastroduodenal ulcer (GU, IVW method, OR = 1.01) (95% CI: 1.00 - 1.01, P = 0.025). The weighted median method produced a similar estimate (OR = 1.01) (95% CI: 1.00 - 1.02; P = 0.019), whereas MR-Egger showed no significant association. No evidence of horizontal pleiotropy was observed. The reverse MR analysis indicated that GU did not have a causal influence on GERD.7 CONCLUSIONS: Our two-sample MR analysis supports the notion that GERD elevates the risk of gastroduodenal ulcers. However, further investigation is needed to elucidate the underlying mechanisms.