Two-sample Mendelian randomization study for schizophrenia and breast cancer

Abstract

Purpose The purpose of this study was to investigate whether the risk of schizophrenia is causally associated with the risk of breast cancer. Methods Bidirectional two-sample Mendelian randomization (TSMR) was performed using genome-wide association study summary data from a total of 311,266 individuals. The causal relationship was estimated using an inverse-variance weighted method (IVW). For sensitivity analysis, weighted median, Mendelian randomization (MR)-Egger regression, and Mendelian randomization Pleiotropy RESidual Sum and Outlier (MR-PRESSO) were used. Results The study showed evidence of a causal association between schizophrenia and the risk of breast cancer. In the IVW analysis, the odds ratio for breast cancer per log odds increase in schizophrenia risk was 1.069 with a 95% confidence interval of 1.028 to 1.112 (P< 0.001). This liability was consistently observed using multiple sensitivity analyses (P< 0.05). By contrast, the TSMR analysis of an inverted direction revealed no significant impact of breast cancer on the risk of schizophrenia. Conclusion Our results suggested that schizophrenia and breast cancer may have shared biological backgrounds. Genetic factors associated with schizophrenia might be causally associated with the risk of breast cancer.

Keywords

• breast neoplasms
• causality
• genetic background
• genome-wide association study
• schizophrenia