Anorexia nervosa and gastrointestinal diseases: A multivariable Mendelian randomization study

Research on the associations between anorexia nervosa (AN) and gastrointestinal (GI) diseases is limited, and the causality and underlying directionality remain unclear. Therefore, we aimed to elucidate the causal associations between AN and the risk of GI diseases through Mendelian randomization (MR) analyses. Summary statistics for AN and 24 GI diseases were obtained from the Psychiatric Genomics Consortium and the public available genome-wide association study databases. Single nucleotide polymorphisms associated with AN and GI diseases at the genome-wide significance level were selected as instrumental variables to perform bidirectional 2-sample MR analyses. Additionally, we performed multivariable MR analyses adjusting for smoking and alcohol consumption. The inverse-variance weighted method was used as the primary MR method, and a series of sensitivity analyses were applied to assess heterogeneity and pleiotropy. Genetically predicted AN showed nominally significant association with higher risk of acute gastritis (OR = 1.593, 95% CI: 1.081-2.347; P = .019) and Crohn disease (OR = 1.001, 95% CI: 1.00008-1.003; P = .038). Reverse MR analyses found a nominally significant positive association between gastric cancer and AN, but no reverse causality was observed for the others. After adjustment for smoking and alcohol consumption, the nominally significant associations of AN with acute gastritis and Crohn disease remained, while the association between gastric cancer and AN became nonsignificant. Our study provides preliminary genetic evidence supporting potential causal associations between AN and specific GI diseases and highlights priority targets for future investigation. Further studies are necessitated to validate these findings and elucidate the underlying mechanisms.