The causality between use of glucocorticoids and risk of pancreatitis: a Mendelian randomization study

Background and aim To date, the association between glucocorticoid use and the risk of pancreatitis remains controversial. The aim of this study was the investigation of this possible relationship. Methods We carried out a two-sample Mendelian randomization (MR) analysis using GWAS data from European ancestry, East Asian descendants and the FinnGen Biobank Consortium to evaluate this potential causal relationship. Genetic variants associated with glucocorticoid use were selected based on genome-wide significance (p 5×10-8). Results Our MR analysis of European ancestry data revealed no significant causal relationship between glucocorticoid use and AP (IVW: OR=1.084, 95% CI= 0.945-1.242, P=0.249; MR-Egger: OR=1.049, 95% CI= 0.686-1.603, P=0.828; weighted median: OR=1.026, 95% CI= 0.863-1.219, P=0.775) or CP (IVW: OR=1.027, 95% CI= 0.850-1.240, P=0.785; MR-Egger: OR= 1.625, 95% CI= 0.913-2.890, P= 0.111; weighted median: OR= 1.176, 95% CI= 0.909-1.523, P= 0.218). Sensitivity analyses, including MR-Egger and MR-PRESSO, indicated no evidence of pleiotropy or heterogeneity, confirming the robustness of our findings. Multivariable MR analysis adjusted for alcohol consumption, BMI, cholelithiasis and C-reactive protein levels supported these findings. Replicated analysis was performed on datasets from the FinnGen Biobank Consortium and East Asian descendants, and similar results were obtained. Conclusions This MR analysis suggests that there is no causal association between glucocorticoid use and the risk of pancreatitis.