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

World J Gastroenterol. 2023 Nov 28;29(44):5872-5881. doi: 10.3748/wjg.v29.i44.5872.

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.

Keywords: Anxiety; Causal effect; Genome-wide association studies; Inflammatory bowel disease; Mendelian randomization.

MeSH terms

  • Adult
  • Anxiety / epidemiology
  • Anxiety / genetics
  • Colitis, Ulcerative* / epidemiology
  • Colitis, Ulcerative* / genetics
  • Crohn Disease* / epidemiology
  • Crohn Disease* / genetics
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Inflammatory Bowel Diseases* / epidemiology
  • Inflammatory Bowel Diseases* / genetics
  • Mendelian Randomization Analysis