Observational and genetic analyses clarify the relationship between type 2 diabetes mellitus and gallstone disease

BackgroundThe relationship between type 2 diabetes mellitus (T2DM) and gallstone disease (GSD) have been incompletely understood. We aimed to investigate their phenotypic and genetic associations and evaluate the biological mechanisms underlying these associations.MethodsWe first evaluated the phenotypic association between T2DM and GSD using data from the UK Biobank (n>450,000) using a prospective observational design. We then conducted genetic analyses using summary statistics from a meta-analysis of genome-wide association studies of T2DM, with and without adjusting for body mass index (BMI) (Ncase=74,124, Ncontrol=824,006; T2DMadjBMI: Ncase=50,409, Ncontrol=523,897) and GSD (Ncase=43,639, Ncontrol=506,798).ResultsA unidirectional phenotypic association was observed, where individuals with T2DM exhibited a higher GSD risk (hazard ratio (HR)=1.39, P