Acute pancreatitis and metabolic syndrome: genetic correlations and causal associations

Abstract

Background: Although there is a definite correlation between the Metabolic Syndrome (MetS) and Acute Pancreatitis (AP), cause is yet unknown. The current work combined linkage disequilibrium score (LDSC) regression and Mendelian randomization (MR) approaches to fill this important information gap.

Methods: In this study, we harnessed the power of publicly available gene-wide association databases (GWAS) to explore the intricate relationship between MetS and its components with AP. The cornerstone of our analysis was the Inverse-Variance Weighted (IVW) method, serving as our primary analytical tool. In addition to IVW, we complemented our investigation with several other robust MR methods, including MR-Egger, Weighted Median, Maximum Likelihood, and MR-PRESSO. By employing this diverse set of analytical approaches, we sought to ensure the comprehensiveness and robustness of our findings.

Result: LDSC regression indicated a genetic correlation between MetS and AP. Univariate MR results indicated a genetic association between MetS (OR = 1.084; 95% CI, 1.005-1.170; P = 0.037), BMI (OR = 1.459; 95% CI, 1.325-1.606; P = 1.46E-14), WHR (OR = 1.189; 95% CI, 1.068-1.323; P = 1.56 E-03), TG (OR = 1.110; 95% CI, 1.001-1.231; P = 0.047), and FI (OR = 1.798; 95% CI, 1.245-2.595; P = 1.74E-03) were able to significantly increase the risk of AP. The results of multivariate MR analysis revealed that these causality associations still existed.

Conclusion: Our investigation has yielded compelling evidence that substantiates the presence of both a genetic correlation and a causal relationship between MetS and AP.

Keywords: Acute pancreatitis; Body Mass Index; Linkage disequilibrium score regression; Mendelian randomization; Metabolic syndrome.