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

Abstract

A correlation has been reported to exist between exposure factors (e.g. liver function) and acute pancreatitis. However, the specific causal relationship remains unclear. This study aimed to infer the causal relationship between liver function and acute pancreatitis using the Mendelian randomisation method. We employed summary data from a genome-wide association study involving individuals of European ancestry from the UK Biobank and FinnGen. Single-nucleotide polymorphisms (SCNPs), closely associated with liver function, served as instrumental variables. We used five regression models for causality assessment: MR-Egger regression, the random-effect inverse variance weighting method (IVW), the weighted median method (WME), the weighted model, and the simple model. We assessed the heterogeneity of the SNPs using Cochran's Q test. Multi-effect analysis was performed using the intercept term of the MR-Egger method and leave-one-out detection. Odds ratios (ORs) were used to evaluate the causal relationship between liver function and acute pancreatitis risk. A total of 641 SNPs were incorporated as instrumental variables. The MR-IVW method indicated a causal effect of gamma-glutamyltransferase (GGT) on acute pancreatitis (OR = 1.180, 95%CI [confidence interval]: 1.021-1.365, P = 0.025), suggesting that GGT may influence the incidence of acute pancreatitis. Conversely, the results for alkaline phosphatase (ALP) (OR = 0.997, 95%CI: 0.992-1.002, P = 0.197) and aspartate aminotransferase (AST) (OR = 0.939, 95%CI: 0.794-1.111, P = 0.464) did not show a causal effect on acute pancreatitis. Additionally, neither the intercept term nor the zero difference in the MR-Egger regression attained statistical significance (P = 0.257), and there were no observable gene effects. This study suggests that GGT levels are a potential risk factor for acute pancreatitis and may increase the associated risk. In contrast, ALP and AST levels did not affect the risk of acute pancreatitis.

• Authors: Chun Zhang, Feng Lin, Deng-Fang Guo, Qing-Lin Wang, De-Xian Xiao, Jian-Yuan Lin, Shi Chen
• Journal: PloS one (PLoS One) Vol. 19 Issue 4 Pg. e0300890 ( 2024) ISSN: 1932-6203 [Electronic] United States
• PMID: 38578756 (Publication Type: Journal Article)
• Copyright: Copyright: © 2024 Zhang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Chemical References

• Alkaline Phosphatase
• Coloring Agents
• Nonoxynol
• gamma-Glutamyltransferase

Topics

• Humans
• Pancreatitis (genetics)
• Acute Disease
• Genome-Wide Association Study
• Causality
• Alkaline Phosphatase (genetics)
• Coloring Agents
• Nonoxynol
• gamma-Glutamyltransferase
• Liver
• Mendelian Randomization Analysis