A genetic data-based causal exploration of the relationship between docosahexaenoic acid levels and the risk of acute pancreatitis

This study investigates the potential causal relationship between docosahexaenoic acid levels and acute pancreatitis (AP) using a 2-sample Mendelian randomization (MR) approach and summary statistics from multiple independent Genome-Wide Association Study databases. The docosahexaenoic acid levels of 1,15,006 individuals of European descent were analyzed; 4,79,902 samples, including 3798 cases of AP and 4,76,104 healthy controls. Docosahexaenoic acid levels were used as the exposure and AP as the outcome. Single nucleotide polymorphisms significantly associated with docosahexaenoic acid levels were selected as instrumental variables. A significant negative correlation was found between docosahexaenoic acid levels and the risk of AP (P = .019, odds ratio [95% confidence interval] = 0.841 [0.727-0.972]), indicating that docosahexaenoic acid serves as an independent protective factor against AP. Sensitivity analyses detected heterogeneity (Q values of 72.48 and 72.65 with P-values of .002 and .003 for MR-Egger and inverse variance weighted, respectively), suggesting the presence of unmeasured confounding factors or pleiotropy. However, no significant pleiotropic effects were identified (MR-Egger intercept P = .754) and MR-Pleiotropy RESidual Sum and Outlier analysis confirmed the absence of outliers (P = .806). The results demonstrated a causal link between genetically predicted docosahexaenoic acid levels and reduced AP risk, offering insights into the prevention and treatment of this condition.