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dc.contributor.authorRuth, Katherine Sen
dc.contributor.authorDay, Felixen
dc.contributor.authorTyrrell, Jessicaen
dc.contributor.authorThompson, Deborah Jen
dc.contributor.authorWood, Andrew Ren
dc.contributor.authorMahajan, Anubhaen
dc.contributor.authorBeaumont, Robin Nen
dc.contributor.authorWittemans, Lauraen
dc.contributor.authorMartin, Susanen
dc.contributor.authorBusch, Alexander Sen
dc.contributor.authorErzurumluoglu, A Mesuten
dc.contributor.authorHollis, Benjaminen
dc.contributor.authorO'Mara, Tracy Aen
dc.contributor.authorEndometrial Cancer Association Consortium,en
dc.contributor.authorMcCarthy, Mark Ien
dc.contributor.authorLangenberg, Claudiaen
dc.contributor.authorEaston, Douglasen
dc.contributor.authorWareham, Nicholasen
dc.contributor.authorBurgess, Stephenen
dc.contributor.authorMurray, Annaen
dc.contributor.authorOng, Kennethen
dc.contributor.authorFrayling, Timothy Men
dc.contributor.authorPerry, Johnen
dc.date.accessioned2019-12-13T00:30:18Z
dc.date.available2019-12-13T00:30:18Z
dc.date.issued2020-02-10en
dc.identifier.issn1078-8956
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/299833
dc.description.abstractTestosterone supplementation is commonly used for its effects on sexual function, bone health and body composition, yet its effects on disease outcomes are unknown. To better understand this, we identified genetic determinants of testosterone levels and related sex hormone traits in 425,097 UK Biobank study participants. Using 2,571 genome-wide significant associations, we demonstrate the genetic determinants of testosterone levels are substantially different between sexes, and that genetically higher testosterone is harmful for metabolic diseases in women but beneficial in men. For example, a genetically determined 1-standard deviation higher testosterone increases the risks of Type 2 diabetes (T2D) (OR=1.37 [1.22–1.53]) and polycystic ovary syndrome (OR=1.51 [1.33–1.72]) in women, but reduces T2D risk in men (OR=0.86 [0.76–0.98]). We also show adverse effects of higher testosterone on breast and endometrial cancers in women, and prostate cancer in men. Our findings provide insights into the disease impacts of testosterone and highlight the importance of sex-specific genetic analyses.
dc.description.sponsorshipA.R.W. and T.M.F. are supported by the European Research Council grant: SZ-245 50371-GLUCOSEGENES-FP7-IDEAS-ERC. R.B. is funded by the Wellcome Trust and Royal Society grant 104150/Z/14/Z. J.T. is supported by the Academy of Medical Sciences Springboard award which is supported by the Wellcome Trust and GCRF [SBF004\1079]. This work was supported by the Medical Research Council [Unit Programme numbers MC_UU_12015/1 and MC_UU_12015/2].
dc.format.mediumPrint-Electronicen
dc.languageengen
dc.publisherSpringer Nature
dc.rightsAll rights reserved
dc.rights.uri
dc.subjectEndometrial Cancer Association Consortiumen
dc.subjectHumansen
dc.subjectPolycystic Ovary Syndromeen
dc.subjectBreast Neoplasmsen
dc.subjectEndometrial Neoplasmsen
dc.subjectProstatic Neoplasmsen
dc.subjectDiabetes Mellitus, Type 2en
dc.subjectTestosteroneen
dc.subjectEstradiolen
dc.subjectCluster Analysisen
dc.subjectOdds Ratioen
dc.subjectSex Factorsen
dc.subjectBody Compositionen
dc.subjectGenotypeen
dc.subjectHaplotypesen
dc.subjectPhenotypeen
dc.subjectPolymorphism, Single Nucleotideen
dc.subjectSoftwareen
dc.subjectBiological Specimen Banksen
dc.subjectFemaleen
dc.subjectMaleen
dc.subjectGenome-Wide Association Studyen
dc.subjectMendelian Randomization Analysisen
dc.subjectBiomarkersen
dc.subjectUnited Kingdomen
dc.titleUsing human genetics to understand the disease impacts of testosterone in men and women.en
dc.typeArticle
prism.endingPage258
prism.issueIdentifier2en
prism.publicationDate2020en
prism.publicationNameNature medicineen
prism.startingPage252
prism.volume26en
dc.identifier.doi10.17863/CAM.46906
dcterms.dateAccepted2020-01-03en
rioxxterms.versionofrecord10.1038/s41591-020-0751-5en
rioxxterms.versionAM
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserveden
rioxxterms.licenseref.startdate2020-02-10en
dc.contributor.orcidDay, Felix [0000-0003-3789-7651]
dc.contributor.orcidWood, Andrew R [0000-0003-1726-948X]
dc.contributor.orcidMartin, Susan [0000-0001-8746-0947]
dc.contributor.orcidBusch, Alexander S [0000-0003-4417-569X]
dc.contributor.orcidErzurumluoglu, A Mesut [0000-0003-1322-8138]
dc.contributor.orcidO'Mara, Tracy A [0000-0002-5436-3232]
dc.contributor.orcidLangenberg, Claudia [0000-0002-5017-7344]
dc.contributor.orcidEaston, Douglas [0000-0003-2444-3247]
dc.contributor.orcidWareham, Nicholas [0000-0003-1422-2993]
dc.contributor.orcidBurgess, Stephen [0000-0001-5365-8760]
dc.contributor.orcidOng, Kenneth [0000-0003-4689-7530]
dc.contributor.orcidFrayling, Timothy M [0000-0001-8362-2603]
dc.contributor.orcidPerry, John [0000-0001-6483-3771]
dc.identifier.eissn1546-170X
rioxxterms.typeJournal Article/Reviewen
pubs.funder-project-idMRC (MC_UU_12015/2)
pubs.funder-project-idMRC (MC_UU_12015/1)
pubs.funder-project-idDepartment of Health (via National Institute for Health Research (NIHR)) (NF-SI-0617-10149)
pubs.funder-project-idMRC (MC_PC_13048)
pubs.funder-project-idMedical Research Council (MC_UU_00002/7)
pubs.funder-project-idMRC (MC_UU_00006/2)
cam.orpheus.successTue Mar 31 10:38:05 BST 2020 - Embargo updated*
cam.orpheus.counter2*
rioxxterms.freetoread.startdate2020-08-10


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