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.
Competing Interests: Conflict of interest: Outside of the current work, MH reports research grants from Boehringer Ingelheim and Sanofi to the University Hospital of Tübingen, participation in advisory board for Boehringer Ingelheim, Sanofi, and Amryt, and lecture fees from Amryt, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Novartis, Novo Nordisk, and Sanofi. L.W. provided consulting service to Pupil Bio, Inc. and reviewed manuscripts for Gastroenterology Report, and received honorarium.