Association of demographic and clinical factors with risk of acute pancreatitis: An exposure‐wide Mendelian randomization study. Issue 1 (7th November 2022)

• Record Type: Journal Article
• Authors: Tang, Qiu‐Yi; Yang, Qi; Yu, Xian‐Qiang; Liu, Yu‐Xiu; Tong, Zhi‐Hui; Li, Bai‐Qiang; Chen, Ya‐Ting; Yu, Evan Yi‐Wen; Li, Wei‐Qin
• Is Part Of: Molecular genetics & genomic medicine. Volume 11:Issue 1(2023)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2022-11-07
• Subjects: Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.2091
• Languages: English
• ISSNs: 2324-9269

Abstract

Abstract: Background: The incidence of acute pancreatitis (AP) is increasing over years, which brings enormous economy and health burden. However, the aetiologies of AP and underlying mechanisms are still unclear. Here, we performed a two‐sample Mendelian randomization (MR) analysis to investigate the associations between all reported possible risk factors and AP using publicly available genome‐wide association study summary statistics. Methods: A series of quality control steps were taken in our analysis to select eligible instrumental single nucleotide polymorphisms which were strongly associated with exposures. To make the conclusions more robust and reliable, we utilized several analytical methods (inverse‐variance weighting, MR‐PRESSO method, weighted median, MR‐Egger regression) that are based on different assumptions of two‐sample MR analysis. The MR‐Egger intercept test, radial regression and leave‐one‐out sensitivity analysis were performed to evaluate the horizontal pleiotropy, heterogeneities, and stability of these genetic variants on each exposure. A two‐step MR method was applied to explore mediators in significant associations. Results: Genetic predisposition to cholelithiasis (effect estimate: 17.30, 95% CI: 12.25–22.36, p = 1.95 E‐11), body mass index (0.32, 95% CI: 0.13–0.51, p < 0.001), body fat percentage (0.57, 95% CI: 0.31–0.83, p = 1.31 E‐05), trunk fat percentage (0.36, 95% CI: 0.14–0.59, p < 0.005), ever smoked (1.61, 95% CI: 0.45–2.77, p = 0.007), and limbs fat percentage (0.55, 95% CI: 0.41–0.69, p < 0.001) were associated with an increased risk of AP. In addition, whole‐body fat‐free mass (−0.32, 95% CI: −0.55 to −0.10, p = 0.004) was associated with a decrease risk of AP. Conclusion: Genetic predisposition to cholelithiasis, obesity and smoking could be causally associated with an increased risk of AP, and whole body fat‐free mass could be associated with a decreased risk of AP. Abstract : The incidence of acute pancreatitis is increasing over years especially in western countries, but the etiologies of acute pancreatitis have not been well understood. And it is unclear whether the reported possible risk factors are real causes of acute pancreatitis. To our knowledge, our research is the first to explore the associations of all reported possible risk factors and acute pancreatitis using public data from the UK biobank and the FinnGen consortium.