The genetic interplay between psychiatric disorders and breast cancer risk: A bidirectional Mendelian randomization study

Background: Evidence of the association between psychiatric disorders, and breast cancer have been inconsistent, and their interpretation often encounters confounding factors. In this study, we used bidirectional Mendelian randomization (MR) analysis to explore the genetic relationships between them. Methods: We performed an MR analysis using publicly available genome-wide association studies of European ancestry to simultaneously examine the relationship between psychiatric disorders, and breast cancer risk. The inverse-variance weighted method for the assessment of the risk psychiatric disorders bring to breast cancer. Weighted media, and MR-Egger regression were used as sensitivity analyses. Results: The MR analysis revealed that major depressive disorder (MDD) may increase the risk of overall breast cancer (odds ratio [OR] = 1.095, 95% confidence interval [CI] = 1.019-1.277, P = 0.014), but not the subtype of breast cancer. Schizophrenia (SCZ) was a risk factor for overall breast cancer (OR = 1.031, 95%CI = 1.012-1.050, P = 0.002), ER+ breast cancer (OR = 1.034, 95%CI = 1.012-1.057, P = 0.002) and ER- breast cancer (OR = 1.050, 95%CI = 1.017-1.084, P = 0.003). However, patients with breast cancer are less likely to have the risk of MDD and SCZ. Conclusion: Our results found that MDD may be a risk factor for overall breast cancer but is not related to its subtypes. SCZ may increase the risk of breast cancer and its subtypes.