Causal association between psycho-psychological factors, such as stress, anxiety, depression, and irritable bowel syndrome: Mendelian randomization

BACKGROUND: Pathogenesis, diagnosis, and treatment of irritable bowel syndrome (IBS) have been reported to be challenging hotspots in clinical practice. Previous observational studies have found that stress, anxiety, depression, and other mental and psychological diseases are closely associated with IBS. This study aimed to further explore the causal relationships of these associations through Mendelian randomization (MR). METHODS: The data needed for MR were obtained from publicly published genome-wide association databases. We performed a bidirectional, 2-sample MR analysis using instrumental variables (IV) associated with stress, anxiety, and depression, and other mental and psychological factors as exposures and IBS as the outcome. A reverse MR analysis with IBS as exposure and stress, anxiety, depression, and other mental and psychological factors as the outcomes was also performed. The inverse variance weighting (IVW) method was adopted as the main method of MR, and the causal effect between stress, anxiety, depression, and other mental and psychological factors and IBS was evaluated as the main result of the study. In addition, a series of sensitivity analyses was conducted to comprehensively evaluate the causal relationship between them. RESULTS: Stress, anxiety, depression, and other mental and psychological factors were the underlying etiologies for IBS (odds ratio [OR] = 1.06, 95% confidence interval [CI]: 1.03–1.08), and they were positively correlated. Univariate analysis further supported the above conclusions (Depression, [OR = 1.31, 95% CI: 1.05–1.63, P = .016], Anxiety, [OR = 1.53, 95% CI: 1.16–2.03, P = .003]). However, in reverse MR analysis, we found that IBS did not affect stress, anxiety, depression, or other mental and psychological factors and that there was no causal relationship between IBS and stress, anxiety, depression, or other mental and psychological factors (P > .05). CONCLUSION: This study demonstrates that mental and psychological factors are the underlying etiologies for IBS. These findings may provide important information for physicians regarding the clinical treatment of IBS.