Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2019 Oct 24;45(6):1251-1256.
doi: 10.1093/schbul/sby162.

Is Schizophrenia a Risk Factor for Breast Cancer?-Evidence From Genetic Data

Enda M Byrne  1 , Manuel A R Ferreira  2 , Angli Xue  1 , Sara Lindström  3 , Xia Jiang  4 , Jian Yang  1   5   6 , Douglas F Easton  7 , Naomi R Wray  1   5 , Georgia Chenevix-Trench  2
Affiliations

Is Schizophrenia a Risk Factor for Breast Cancer?-Evidence From Genetic Data

Enda M Byrne et al. Schizophr Bull. .

Abstract

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 = 40675 cases and 64643 controls) and breast cancer (n = 122977 cases and 105974 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 (rG) between the 2 disorders (rG = 0.14, SE = 0.03, P = 4.75 × 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 (SE = 0.009, P = 2.3 × 10-4). A 1 SD 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, SE = 0.012, P = .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.

Keywords: Mendelian Randomization; causality; epidemiology; genetic correlation; pleiotropy.

PubMed Disclaimer

Figures

Fig. 1.
Fig. 1.
Generalized summary-based Mendelian Randomization (GSMR) plot for schizophrenia as exposure and breast cancer as outcome. Dotted line shows the GSMR estimate of causal effect.
Fig. 2.
Fig. 2.
Generalized summary-based Mendelian Randomization (GSMR) plot for breast cancer as exposure and schizophrenia as outcome.
See this image and copyright information in PMC

References

    1. Nielsen RE, Uggerby AS, Jensen SO, McGrath JJ. Increasing mortality gap for patients diagnosed with schizophrenia over the last three decades–a Danish nationwide study from 1980 to 2010. Schizophr Res. 2013;146:22–27. - PubMed
    1. Hodgson R, Wildgust HJ, Bushe CJ. Cancer and schizophrenia: is there a paradox?J Psychopharmacol. 2010;24:51–60. - PMC - PubMed
    1. Bushe CJ, Bradley AJ, Wildgust HJ, Hodgson RE. Schizophrenia and breast cancer incidence: a systematic review of clinical studies. Schizophr Res. 2009;114:6–16. - PubMed
    1. Grinshpoon A, Barchana M, Ponizovsky A, et al. Cancer in schizophrenia: is the risk higher or lower?Schizophr Res. 2005;73:333–341. - PubMed
    1. Lichtermann D, Ekelund J, Pukkala E, Tanskanen A, Lönnqvist J. Incidence of cancer among persons with schizophrenia and their relatives. Arch Gen Psychiatry. 2001;58:573–578. - PubMed

Publication types