We read with great interest the population-based cohort study by Abrahami D et al,1 in which they found that the use of proton pump inhibitors (PPIs) was not associated with an increased risk of inflammatory bowel disease (IBD). However, the assessment of causality in observational studies is often challenging due to the presence of multiple confounding factors. The existence of a causal relationship between PPIs and IBD remains unclear at present. Mendelian randomisation (MR) is a method of generating more reliable evidence using exposure-related genetic variants to assess causality, limiting the bias caused by confounders.2 Therefore, we used a two-sample MR analysis to investigate the association between the use of PPIs and IBD including Crohn’s disease (CD) and ulcerative colitis (UC).

For this study, different cohort data sources were used for exposure and outcome to avoid sample overlap (online supplemental material). We used summary statistics from the medication use case-control genome-wide association studies conducted among UK Biobank study participants to generate genetic instruments for …