Genetic Evidence for the Association between Schizophrenia and Breast Cancer

Objective: To estimate the potential effect of schizophrenia on breast cancer risk in women, we performed a two-sample Mendelian randomization (MR) study. Methods: The instrumental variables comprised 170 uncorrelated and non-pleiotropic single nucleotide polymorphisms (SNPs) that are significantly associated with schizophrenia risk in genome-wide association studies in 105,000 European descent individuals of the Psychiatric Genomics Consortium (http://www.med.unc.edu/pgc/) and the United Kingdom Clozapine Clinic. The association between these SNPs determined schizophrenia and breast cancer risk was estimated in approximately 229,000 European descent females from the Breast Cancer Association Consortium using the inverse-variance weighted and the weighted median MR methods. Results: We found that the genetically-predicted risk of schizophrenia was associated with increased breast cancer risk (under a random-effects model: odds ratio per 1 unit increase in log odds of schizophrenia = 1.04, 95% confidence interval: 1.02–1.06, p = 5.6 × 10−5). Similar significant associations were observed in analyses using a weighted median model and sensitivity analysis excluding six SNPs with genotype imputation score of less than 0.8, as well as analyses stratified by estrogen receptor status of breast cancer. Conclusion: Our findings implicate a modest increased risk for breast cancer in genetically determined schizophrenic females.