Noncausal effects of genetic predicted depression and colorectal cancer risk: A Mendelian randomization study

Abstract

Depression has been associated with colorectal cancer (CRC) in observational studies. However, the causality of depression on CRC risk remained unknown. This study aimed to evaluate the potential causal association between genetic variants related to depression and the risk of CRC using Mendelian randomization (MR). Two-sample MR analysis using summary data was performed to examine whether depression was causally associated with CRC risk. We used 2 sets of instrumental variables (IV) from the genome-wide association study results for analysis. A set of IV related to major depressive disorder contain 44 single-nucleotide polymorphisms. Another set of IV was related to major depression, including 53 single-nucleotide polymorphisms. Summary data of CRC was from the FinnGen consortium. Based on the results of MR using inverse-variance weighted method, we found that genetically determined major depressive disorder (odds ratio = 1.06, 95% confidence interval = 0.77-1.45) or major depression (odds ratio = 0.77, 95% confidence interval = 0.57-1.04) did not causally increase CRC risk. The results of MR-Egger and the weighted median method are consistent with the inverse-variance weighted method. The two-sample MR analysis showed that depression is not causally associated with CRC risk. Further research is needed to investigate the association between depression and CRC.