Genetically Predicted Visceral Adipose Tissue and Risk of Nine Non-tumor Gastrointestinal Diseases: Evidence from A Mendelian Randomization Study

Abstract

Abstract Background Numerous studies have linked visceral adipose tissue (VAT) to gastrointestinal diseases. However, it remains unclear whether those associations reflect causality. Methods We used a two-sample Mendelian randomization (MR) approach to elucidate the causal effect of VAT on nine non-tumor gastrointestinal diseases. The inverse-variance weighted method was used to perform MR analyses. Complementary MR analyses, sensitivity analyses, and multivariable MR analyses were conducted to confirm the results. Results Genetically predicted higher VAT was causally associated with increased risks of gastro-oesophageal reflux disease (GORD) [odds ratio (OR), 1.21; 95% confidence interval (CI), 1.09–1.34; P = 3.06×10− 4), duodenal ulcer (DU) (OR, 1.40; 95% CI, 1.10–1.77; P = 0.005), cholelithiasis (OR, 1.69; 95% CI, 1.52–1.88; P = 1.70×10− 21), and non-alcoholic fatty liver disease (NAFLD) (OR, 2.68; 95% CI, 1.87–3.82; P = 6.26×10− 8). There were suggestive causal associations between VAT and gastric ulcer (GU) (OR,1.22; 95% CI, 1.01–1.48; P = 0.035) and acute pancreatitis (AP) (OR, 1.26; 95% CI, 1.05–1.52; P = 0.013). Little evidence was observed to support an association between VAT and inflammatory bowel disease, irritable bowel syndrome, or chronic pancreatitis. Conclusions We found that genetically predicted higher VAT was causally associated with increased risks of GORD, GU, DU, cholelithiasis, AP, and NAFLD. Future research is needed to assess the validity of VAT as a risk predictor and examine the mediation processes for potential intervention targets.