Causal relationships between obesity and pancreatobiliary diseases: a two-sample Mendelian randomization study

Abstract Previous observational studies have investigated the relationship between obesity and the biliary tract and pancreas. The causality, however, is still to be confirmed. This study was designed to explore the causality between obesity which included body mass index(BMI), circumference (WC), hip circumference (HC) and waist-to-hip ratio (WHR), and pancreatobiliary diseases with a Two-Sample Mendelian Randomization(MR) analysis. single-nucleotide polymorphisms used in our study were derived from genome-wide association studies (GWAS). The inverse variance weighted was the dominated method to evaluate the causality. The heterogeneity was validated by Cochran's Q test. The pleiotropy was validated by MR-Egger regression and MR-PRESSO. The stability and reliability of the results were illustrated by the ‘leave-one-out’sensitivity analysis. The MR results explored positive causal effects of BMI (OR: 1.021; 95% CI: from 1.016 to 1.027; P = 4.25 × 10 −15 ) and WC (OR: 1.021; 95% CI: from 1.015 to 1.028; P = 1.65 × 10 −10 ) on pancreatobiliary diseases. However, no causality existed between HC, WHR and pancreatobiliary diseases. This study reminded that general obesity and abdominal obesity required weight loss to prevent pancreatic biliary disease.