Mental Health
Causal relationship between schizophrenia and breast cancer: A two-sample Mendelian randomization study and polygenic risk score Ji Su* Ji Su Yang Nan Song Chul-Hyun Cho Chung Mo Nam Hyeon Chang Kim Sun Jae Jung
Introduction
Epidemiological observational research has identified a link between schizophrenia and breast cancer, but findings in Asian contexts show variations. The underlying cause of the higher breast cancer incidence among individuals with schizophrenia remains unclear.
Methods
A two-sample Mendelian randomization (MR) was performed to identify the causal association between schizophrenia and breast cancer. Genetic variants significantly associated with schizophrenia were obtained from the NHGRI-EBI GWAS Catalog. The study population included 2,165 breast cancer patients from the Seoul Breast Cancer Study (SeBCS) and 2,046 healthy controls from the Korea Genome Epidemiology Study (KoGES). A candidate gene association analysis was conducted for both breast cancer cases and controls, followed by MR using inverse variance weighting (IVW), weighted median, and MR-Egger approaches. Radial MR methods were applied to remove outliers and address pleiotropic bias. A polygenic risk score (PRS) was created with schizophrenia-associated SNPs and compared between the breast cancer and control groups.
Results
A causal association between schizophrenia and breast cancer was observed in the IVW method of MR analysis (OR=1.14; 95% CI, 1.01-1.28). The Radial MR analysis detected outliers, and consistent effect estimates were observed after removing these outliers (OR=1.14, 95% CI 1.01-1.28). A significant association was also found between schizophrenia PRS (per 1SD) and breast cancer risk (OR=1.18; 95% CI, 1.12-1.26).
Conclusion
The Mendelian randomization study corroborated findings suggesting a causal relationship between schizophrenia and breast cancer. These findings provide a basis for clinical guidelines addressing the high risk of breast cancer in patients with schizophrenia, including recommendations for breast cancer screening among women with schizophrenia.