Genetic Evidence for a Causal Link between Intra-Pancreatic Fat Deposition and Pancreatitis: a Mendelian Randomization Study

Introduction Recent associative studies have linked intra-pancreatic fat deposition (IPFD) with risk of pancreatitis, but the causal relationship remains unclear. Methods Utilizing Mendelian randomization, we evaluated the causal association between genetically predicted IPFD and pancreatitis. This approach utilized genetic variants from genome-wide association studies of IPFD (n=25,617), acute pancreatitis (n=6,787 cases/361,641 controls), and chronic pancreatitis (n=3,875 cases/361,641 controls). Results Genetically predicted IPFD was significantly associated with acute pancreatitis (OR per 1-SD increase: 1.40[95%CI:1.12-1.76], p=0.0032) and chronic pancreatitis (OR:1.64[95%CI:1.13-2.39], p=0.0097). Discussion Our findings support a causal role of IPFD in pancreatitis, suggesting that reducing IPFD could lower the risk of pancreatitis.