Large-scale genome-wide association studies identified causal relationship between multiple blood biomarkers and risk of acute pancreatitis.

Abstract

Observational studies have shown that there is a connection between blood biomarkers and the occurrence of acute pancreatitis (AP). Nevertheless, the causal relationships are still not clear. The purpose of this study was to evaluate causal association between biomarkers and AP. A bidirectional two-sample Mendelian randomization (MR) analysis was applied to investigate the causal association between blood biomarkers and AP. Summary statistics obtained from genome-wide association studies were utilized for this analysis. The primary statistical approach employed was the inverse variance weighted (IVW) method, complemented by sensitivity analyses aimed at assessing heterogeneity and pleiotropy. Furthermore, a multivariable MR (MVMR) analysis was performed to adjust for confounders. A total of 11 red blood cell (RBC) traits, 6 white blood cell traits, platelet count, and 30 blood biomarkers were analyzed in this study. Genetically predicted RBC count (IVW odds ratio [OR]=1.144, P=0.004), the high light scatter reticulocyte count (HLSR) (OR=1.127, P=0.022), blood glucose (BG) (OR=1.480, P=0.019), and leptin (OR=1.234, P=0.050) were suggestively associated with an increased risk of AP. Reverse MR analysis showed no causal effect of AP on RBC, HLSR, BG, and leptin (IVW P>0.05). Sensitivity analyses and MVMR analysis still supported the earlier causality. Our findings provide evidence of a suggestive association between RBC count, HLSR, BG, and leptin with an increased susceptibility to AP. These findings aid in our comprehension of the cause of AP and may be used as potential prognostic markers or predictors of severity with AP.