Investigating the impact of metabolic syndrome and its components on pancreas fat: a Bidirectional Mendelian randomization study

Objective: Metabolic syndrome (MetS) and fatty pancreas are two prevalent health conditions that are strongly associated with an elevated risk of developing type 2 diabetes, cardiovascular disease, and pancreatic cancer. Understanding the causal relationship between these conditions is important for developing effective prevention and treatment strategies. In this study, we performed a bidirectional Mendelian randomization analysis to investigate the potential causal relationship between MetS and fatty pancreas. Methods: This study undertook bidirectional Mendelian randomization. Genetic instruments for obesity, glycemic, lipid, and blood pressure were identified as instrumental variables for MetS traits in order to evaluate their causal role in pancreatic fat etiology. Summary level data for pancreas fat (PF) were obtained from a genome-wide association study conducted in the UK Biobank. Results: There was no causal relationship between MetS as a binary trait and PF. In addition, a causal association of increasing Waist-to-Hip Ratio (WHR) with pancreatic fat risk was found [odds ratio (OR)=1.173, 95% confidence interval (CI): 1.067-1.288, p=9*10 -4 ]. Notably, there is no evidence of a causal relationship between PF and glycemic, lipid, and blood pressure. Sensitivity analyses did not indicate that pleiotropy was an important source of bias. Conclusion: MetS had no causal relationship with pancreatic fat. Of the components of the metabolic syndrome, only abdominal obesity and pancreatic fat were observed to be causally related.