The Causal Effect of Intra-Pancreatic Fat Deposition on Acute and Chronic Pancreatitis: A Mendelian Randomization Study

INTRODUCTION: Recent associative studies have linked intrapancreatic fat deposition (IPFD) with risk of pancreatitis, but the causal relationship remains unclear. METHODS: Using Mendelian randomization, we evaluated the causal association between genetically predicted IPFD and pancreatitis. This approach used genetic variants from genomewide 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 (odds ratio per 1-SD increase: 1.40 [95% CI: 1.12–1.76], P = 0.0032) and chronic pancreatitis (odds ratio: 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.