Colorectal Cancer and Common Psychiatric Disorders: A Two-sample Mendelian Randomization Study

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Abstract
Objective: This study aimed to elucidate the causal relationships between colorectal cancer (CRC) and prevalent psychiatric disorders using a two-sample Mendelian randomization approach and to provide evidence supporting the gut-brain axis (GBA) hypothesis. Methods: Utilizing publicly available GWAS datasets, we explored the connections between CRC and various psychiatric disorders, including depression, anxiety, bipolar disorder, and schizophrenia. We applied three statistical analyses: inverse variance weighting, MR-Egger, and median weighting. Sensitivity analyses were conducted to ensure the reliability and validity of our results. Results: The inverse variance weighting analysis revealed no significant associations between CRC incidence and depression (OR=0.995, 95% CI: 0.995-1.000, P=0.090), anxiety (OR=1.001, 95% CI: 1.000-1.001, P=0.099), or schizophrenia (OR=1.003, 95% CI: 0.960-1.047, P=0.899). Conversely, a significant inverse relationship was found with bipolar disorder (OR=0.937, 95% CI: 0.8919~0.9849, P=0.010). Conclusion: Our study did not find causal connections between CRC and the psychiatric conditions of depression, anxiety, or schizophrenia. However, the inverse causal relationship between CRC and bipolar disorder highlights the role of the GBA, offering novel insights into the relationship between gastrointestinal cancer and mental health.

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