Assessing the causal link between liver function and acute pancreatitis: A Mendelian randomisation study.

Area of Science:

• Genetics and Epidemiology
• Gastroenterology
• Biomarkers

Background:

• A correlation exists between liver function and acute pancreatitis, but the causal relationship is not well-defined.
• Understanding the causal links is crucial for identifying risk factors and developing preventative strategies for acute pancreatitis.

Purpose of the Study:

• To investigate the potential causal relationship between key liver function markers and the risk of developing acute pancreatitis.
• To utilize Mendelian randomization to infer causality using genetic instrumental variables.

Main Methods:

• Employed Mendelian randomization using summary data from UK Biobank and FinnGen genome-wide association studies.
• Utilized 641 single-nucleotide polymorphisms (SNPs) associated with liver function as instrumental variables.
• Applied five regression models (MR-Egger, IVW, weighted median, weighted, simple) for causality assessment and heterogeneity testing.

Main Results:

• The inverse variance weighting (IVW) method indicated a significant causal effect of gamma-glutamyltransferase (GGT) on acute pancreatitis risk (OR = 1.180, P = 0.025).
• No significant causal effect was observed for alkaline phosphatase (ALP) (OR = 0.997, P = 0.197) or aspartate aminotransferase (AST) (OR = 0.939, P = 0.464).
• MR-Egger regression and leave-one-out analyses confirmed the robustness of the findings and absence of significant pleiotropy.

Conclusions:

• Elevated gamma-glutamyltransferase (GGT) levels represent a potential causal risk factor for acute pancreatitis.
• Alkaline phosphatase (ALP) and aspartate aminotransferase (AST) levels do not appear to causally influence acute pancreatitis risk.
• Mendelian randomization provides valuable insights into the causal underpinnings of liver function markers in disease etiology.