Causal associations between inflammatory bowel disease and anxiety: A bidirectional Mendelian randomization study

Anxiety is common in patients with inflammatory bowel disease (IBD), including those with ulcerative colitis (UC) and Crohn's disease (CD); however, the causal relationship between IBD and anxiety remains unknown.To investigate the causal relationship between IBD and anxiety by using bidirectional Mendelian randomization analysis.Single nucleotide polymorphisms retrieved from genome-wide association studies (GWAS) of the European population were identified as genetic instrument variants. GWAS statistics for individuals with UC (6968 patients and 20464 controls; adults) and CD (5956 patients and 14927 controls; adults) were obtained from the International IBD Genetics Consortium. GWAS statistics for individuals with anxiety were obtained from the Psychiatric Genomics Consortium (2565 patients and 14745 controls; adults) and FinnGen project (20992 patients and 197800 controls; adults), respectively. Inverse-variance weighted was applied to assess the causal relationship, and the results were strengthened by heterogeneity, pleiotropy and leave-one-out analyses.Genetic susceptibility to UC was associated with an increased risk of anxiety [odds ratio: 1.071 (95% confidence interval: 1.009-1.135), P = 0.023], while genetic susceptibility to CD was not associated with anxiety. Genetic susceptibility to anxiety was not associated with UC or CD. No heterogeneity or pleiotropy was observed, and the leave-one-out analysis excluded the potential influence of a particular variant.This study revealed that genetic susceptibility to UC was significantly associated with anxiety and highlighted the importance of early screening for anxiety in patients with UC.