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

Abstract

BACKGROUND 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. AIM To investigate the causal relationship between IBD and anxiety by using bidirectional Mendelian randomization analysis. METHODS 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. RESULTS 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. CONCLUSION 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.