F-statistic.

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.

已有研究报道，暴露因素（如肝功能）与急性胰腺炎之间存在相关性，但二者间的具体因果关联仍不明确。本研究旨在采用孟德尔随机化（Mendelian randomisation）方法，推断肝功能与急性胰腺炎之间的因果关联。本研究使用了来自英国生物库（UK Biobank）与FinnGen的欧洲血统人群的全基因组关联研究（genome-wide association study）汇总数据。与肝功能紧密相关的单核苷酸多态性（Single-nucleotide polymorphisms, SCNPs）被用作工具变量。本研究采用5种回归模型开展因果关联评估：MR-Egger回归、随机效应逆方差加权法（IVW）、加权中位数法（WME）、加权模型与简单模型。本研究采用Cochran Q检验对单核苷酸多态性的异质性进行评估。通过MR-Egger法的截距项与留一法检测开展多效性分析。本研究采用比值比（Odds ratios, ORs）评估肝功能与急性胰腺炎发病风险之间的因果关联。最终共纳入641个单核苷酸多态性作为工具变量。MR-IVW法结果显示，γ-谷氨酰转移酶（gamma-glutamyltransferase, GGT）对急性胰腺炎存在因果效应（OR=1.180，95%置信区间[CI]：1.021~1.365，P=0.025），提示GGT可能影响急性胰腺炎的发病风险。与之相反，碱性磷酸酶（alkaline phosphatase, ALP）（OR=0.997，95%置信区间[CI]：0.992~1.002，P=0.197）与天冬氨酸氨基转移酶（aspartate aminotransferase, AST）（OR=0.939，95%置信区间[CI]：0.794~1.111，P=0.464）的分析结果均未显示其对急性胰腺炎存在因果效应。此外，MR-Egger回归的截距项与零差异均未达到统计学显著性（P=0.257），未观察到基因多效性。本研究表明，GGT水平是急性胰腺炎的潜在危险因素，可能升高其发病风险；与之相反，ALP与AST水平并未对急性胰腺炎的发病风险产生影响。