Is schizophrenia a risk factor for breast cancer? – Evidence from genetic data

Easton, DF 

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Observational epidemiological studies have found an association between schizophrenia and breast cancer, but it is not known if the relationship is a causal one. We used summary statistics from very large genome-wide association studies of schizophrenia (n = 40,675 cases and 64,643 controls) and breast cancer (n = 122,977 cases and 105,974 controls) to investigate whether there is evidence that the association is partly due to shared genetic risk factors and whether there is evidence of a causal relationship. Using LD-score regression, we found that there is a small but significant genetic correlation between the two disorders (rG = 0.14, S.E = 0.03, p = 4.75 x 10-8), indicating shared genetic risk factors. Using 142 genetic variants associated with schizophrenia as instrumental variables that are a proxy for having schizophrenia, we estimated a causal effect of schizophrenia on breast cancer on the observed scale as bxy = 0.032 (S.E. = 0.009, p = 2.3 x 10-4). A one standard deviation increase in liability to schizophrenia increases risk of breast cancer 1.09-fold. In contrast, the estimated causal effect of breast cancer on schizophrenia from 191 instruments was not significantly different from zero (bxy = -0.005, S.E. = 0.012, p =0.67). No evidence for pleiotropy was found and adjusting for the effects of smoking or parity did not alter the results. These results provide evidence that the previously observed association is due to schizophrenia causally increasing risk for breast cancer. Genetic variants may provide an avenue to elucidating the mechanism underpinning this relationship.

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Mendelian Randomization, causality, epidemiology, genetic correlation, pleiotropy, Breast Neoplasms, Female, Genome-Wide Association Study, Humans, Mendelian Randomization Analysis, Parity, Polymorphism, Single Nucleotide, Risk Factors, Schizophrenia, Smoking
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Schizophrenia Bulletin
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Oxford University Press
National Cancer Institute (R01CA128978)
National Cancer Institute (U19CA148065)
European Commission (223175)
European Commission Horizon 2020 (H2020) Societal Challenges (634935)
European Commission Horizon 2020 (H2020) Societal Challenges (633784)
Cancer Research UK (A10710)
Cancer Research UK (A16563)
Cancer Research UK (A12014)
Cancer Research UK (A10118)