Background Obesity has been established as a risk factor for several gastrointestinal diseases, whether the associations are causal is uncertain. In addition, the associations of obesity-related factors with gastrointestinal diseases have been scarcely explored. This Mendelian randomization aimed to investigate the associations of birth weight, childhood body mass index (BMI), adulthood BMI and waist-hip ratio, and body composition with the risk of 24 gastrointestinal diseases.

Methods Independent 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 and large consortia.

Results Genetically predicted higher levels of birth weight was associated with a lower risk of gastroesophageal reflux. Genetically predicted higher childhood BMI was associated with an increased risk of duodenal ulcer, non-alcoholic 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 18 gastrointestinal diseases. There were no strong associations between genetically predicted whole body fat and fat-free mass indices with gastrointestinal diseases.

Conclusion This 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.

The authors have declared no competing interest.

XL: the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001). MZD: Natural Science Foundation of Hunan Province (2021JJ30999); SCL: the Swedish Heart Lung Foundation (20210351), the Swedish Research Council (2019-00977), and the Swedish Cancer Society (Cancerfonden). Funders had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.

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