AbstractObjectiveThis Mendelian randomization study aimed to investigate the associations of birth weight, childhood BMI, and adulthood BMI, waist‐hip ratio, and body composition with the risk of 24 gastrointestinal diseases.MethodsIndependent genetic instruments associated with the exposures at the genome‐wide significance level (p < 5 × 10⁻⁸) were selected from corresponding large‐scale genome‐wide association studies. Summary‐level data for gastrointestinal diseases were obtained from the UK Biobank, the FinnGen study, and large consortia of European ancestry.ResultsGenetically predicted higher levels of birth weight were associated with a lower risk of gastroesophageal reflux. Genetically predicted higher childhood BMI was associated with an increased risk of duodenal ulcer, nonalcoholic fatty liver disease, and cholelithiasis. However, the associations did not persist after adjusting for genetically predicted adulthood BMI. Genetically predicted higher adulthood BMI and waist‐hip ratio were associated with 19 and 17 gastrointestinal diseases, respectively. Genetically predicted greater visceral adiposity was associated with an increased risk of 17 gastrointestinal diseases. There were no strong associations among genetically predicted whole‐body fat and fat‐free mass indices with gastrointestinal diseases.ConclusionsThis study suggests that greater adulthood adiposity, measured as either BMI, waist‐hip ratio, or visceral adipose tissue, is causally associated with an increased risk of a broad range of gastrointestinal diseases in the European population.