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 phycological 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 (MR) method to investigate the association between phycological disorders and functional gastrointestinal disorders (FGIDs). Methods: : We obtained genome-wide association study (GWAS) summary statistics for two common phycological disorders (depression and anxiety) and three common FGIDs (functional dyspepsia (FD), constipation and irritable bowel syndrome (IBS)) from several publicly available GWAS databases. The inverse variance weighted (IVW) method was used as the main MR method. Results: : IVW MR analyses showed statistically significant associations between genetically predicted depression and risk of FD (OR 1.40, 95%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 higher risk of IBS (OR 1.13, 95%CI 1.10-1.17) instead of FD and constipation. Additionally, genetically predicted IBS instead of FD and constipation was associated with higher risk of depression (OR 1.33, 95%CI 1.12-1.57) and anxiety (OR 2.05, 95%CI 1.05-4.03). Conclusions: : Depression is a causal risk factor for three common FGIDs. A bidirectional causal relationship between IBS and anxiety or depression was also identified.