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

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cam.issuedOnline2018-11-19
dc.contributor.authorEaston, DF
dc.contributor.orcidEaston, Douglas [0000-0003-2444-3247]
dc.date.accessioned2018-12-19T00:30:33Z
dc.date.available2018-12-19T00:30:33Z
dc.date.issued2019-10-24
dc.description.abstractObservational 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.
dc.identifier.doi10.17863/CAM.34468
dc.identifier.eissn1745-1701
dc.identifier.issn1745-1701
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/287159
dc.language.isoeng
dc.publisherOxford University Press
dc.publisher.urlhttp://dx.doi.org/10.1093/schbul/sby162
dc.subjectMendelian Randomization
dc.subjectcausality
dc.subjectepidemiology
dc.subjectgenetic correlation
dc.subjectpleiotropy
dc.subjectBreast Neoplasms
dc.subjectFemale
dc.subjectGenome-Wide Association Study
dc.subjectHumans
dc.subjectMendelian Randomization Analysis
dc.subjectParity
dc.subjectPolymorphism, Single Nucleotide
dc.subjectRisk Factors
dc.subjectSchizophrenia
dc.subjectSmoking
dc.titleIs schizophrenia a risk factor for breast cancer? – Evidence from genetic data
dc.typeArticle
dcterms.dateAccepted2018-10-22
prism.publicationNameSchizophrenia Bulletin
pubs.funder-project-idNational Cancer Institute (R01CA128978)
pubs.funder-project-idNational Cancer Institute (U19CA148065)
pubs.funder-project-idEuropean Commission (223175)
pubs.funder-project-idEuropean Commission Horizon 2020 (H2020) Societal Challenges (634935)
pubs.funder-project-idEuropean Commission Horizon 2020 (H2020) Societal Challenges (633784)
pubs.funder-project-idCancer Research UK (10710)
pubs.funder-project-idCancer Research UK (16563)
pubs.funder-project-idCancer Research UK (12014)
pubs.funder-project-idCancer Research UK (10118)
pubs.funder-project-idNational Cancer Institute (U19CA148537)
pubs.funder-project-idEuropean Commission (16563)
pubs.funder-project-idCancer Research Uk (None)
pubs.funder-project-idCancer Research UK (16565)
rioxxterms.licenseref.startdate2018-10-22
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review
rioxxterms.versionAM
rioxxterms.versionofrecord10.1093/schbul/sby162

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