Integration of observational and causal evidence for the association between adiposity and 17 gastrointestinal outcomes: An umbrella review and meta-analysis

We systematically reviewed observational and Mendelian randomization (MR) articles that evaluated the association between obesity and 17 gastrointestinal (GI) diseases to integrate causal and observational evidence. A total of 594 observational studies from 26 systematic reviews and meta-analyses and nine MR articles were included. For every 5 kg/m² increase in body mass index (BMI), there was an increased risk of GI diseases ranging from 2% for rectal cancer (relative risk [RR]: 1.02, 95% confidence interval [CI]: 1.01 to 1.03) to 63% for gallbladder disease (RR: 1.63, 95% CI: 1.50 to 1.77). MR articles indicated that risks of developing GI diseases elevated with each 1 standard deviation increase in genetically predicted BMI, ranging from 11% for Crohn's disease to 189% for nonalcoholic fatty liver disease. Moreover, upper GI conditions were less susceptible, whereas hepatobiliary organs were more vulnerable to increased adiposity. Among the associations between obesity and the 17 GI conditions, causal relationships were inferred from only approximately half (10/17, 59%). This study reveals a substantial gap between observational and causal evidence, indicating that a combined approach is necessary to effectively inform public health policies and guide epidemiological research on obesity and GI diseases.