Causal relationships between psychological disorders and functional gastrointestinal disorders: a bidirectional two-sample Mendelian randomization study

Background and Aims: Observational studies have shown bidirectional associations between psychological disorders (e.g. depression and anxiety) and functional gastrointestinal disorders. However, whether the relationships are causal is uncertain. Here, we used a bidirectional two-sample Mendelian randomization method to investigate the association between psychological disorders and functional gastrointestinal disorders (FGIDs). Methods We obtained genome-wide association study summary statistics for two common psychological disorders: depression (170 756 cases) and anxiety (31 977 cases), as well as for three common FGIDs: functional dyspepsia with 6666 cases, constipation with 26 919 cases, and irritable bowel syndrome (IBS) with 7053 cases. These summary statistics were retrieved from several publicly available genome-wide association study databases. The inverse variance weighted method was used as the main Mendelian randomization method. Results Inverse variance weighted Mendelian randomization analyses showed statistically significant associations between genetically predicted depression and risk of functional dyspepsia [odds ratio (OR): 1.40, 95% confidence interval (CI): 1.08–1.82], constipation (OR: 1.28, 95% CI: 1.13–1.44), and IBS (OR: 1.51, 95% CI: 1.37–1.67). Genetically predicted anxiety was associated with a higher risk of IBS (OR: 1.13, 95% CI: 1.10–1.17) instead of functional dyspepsia and constipation. In addition, genetically predicted IBS instead of functional dyspepsia and constipation was associated with a higher risk of depression (OR: 1.33, 95% CI: 1.12–1.57) and anxiety (OR: 2.05, 95% CI: 1.05–4.03). Conclusion Depression is a causal risk factor for three common FGIDs. A bidirectional causal relationship between IBS and anxiety or depression was also identified.