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dc.contributor.authorKarunamuni, RA
dc.contributor.authorHuynh-Le, M-P
dc.contributor.authorFan, CC
dc.contributor.authorThompson, W
dc.contributor.authorLui, A
dc.contributor.authorMartinez, ME
dc.contributor.authorRose, BS
dc.contributor.authorMahal, B
dc.contributor.authorEeles, RA
dc.contributor.authorKote-Jarai, Z
dc.contributor.authorMuir, K
dc.contributor.authorLophatananon, A
dc.contributor.authorUKGPCS Collaborators
dc.contributor.authorTangen, CM
dc.contributor.authorGoodman, PJ
dc.contributor.authorThompson, IM
dc.contributor.authorBlot, WJ
dc.contributor.authorZheng, W
dc.contributor.authorKibel, AS
dc.contributor.authorDrake, BF
dc.contributor.authorCussenot, O
dc.contributor.authorCancel-Tassin, G
dc.contributor.authorMenegaux, F
dc.contributor.authorTruong, T
dc.contributor.authorPark, JY
dc.contributor.authorLin, H-Y
dc.contributor.authorTaylor, JA
dc.contributor.authorBensen, JT
dc.contributor.authorMohler, JL
dc.contributor.authorFontham, ETH
dc.contributor.authorMultigner, L
dc.contributor.authorBlanchet, P
dc.contributor.authorBrureau, L
dc.contributor.authorRomana, M
dc.contributor.authorLeach, RJ
dc.contributor.authorJohn, EM
dc.contributor.authorFowke, JH
dc.contributor.authorBush, WS
dc.contributor.authorAldrich, MC
dc.contributor.authorCrawford, DC
dc.contributor.authorCullen, J
dc.contributor.authorPetrovics, G
dc.contributor.authorParent, M-É
dc.contributor.authorHu, JJ
dc.contributor.authorSanderson, M
dc.contributor.authorPRACTICAL Consortium
dc.contributor.authorMills, IG
dc.contributor.authorAndreassen, OA
dc.contributor.authorDale, AM
dc.contributor.authorSeibert, TM
dc.date.accessioned2022-01-25T11:35:13Z
dc.date.available2022-01-25T11:35:13Z
dc.date.issued2021-06-14
dc.identifier.citationProstate cancer and prostatic diseases, 2021en_US
dc.identifier.issn1365-7852
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/4969
dc.identifier.eissn1476-5608en_US
dc.identifier.eissn1476-5608
dc.identifier.doi10.1038/s41391-021-00403-7en_US
dc.identifier.doi10.1038/s41391-021-00403-7
dc.description.abstract<h4>Background</h4>We previously developed an African-ancestry-specific polygenic hazard score (PHS46+African) that substantially improved prostate cancer risk stratification in men with African ancestry. The model consists of 46 SNPs identified in Europeans and 3 SNPs from 8q24 shown to improve model performance in Africans. Herein, we used principal component (PC) analysis to uncover subpopulations of men with African ancestry for whom the utility of PHS46+African may differ.<h4>Materials and methods</h4>Genotypic data were obtained from the PRACTICAL consortium for 6253 men with African genetic ancestry. Genetic variation in a window spanning 3 African-specific 8q24 SNPs was estimated using 93 PCs. A Cox proportional hazards framework was used to identify the pair of PCs most strongly associated with the performance of PHS46+African. A calibration factor (CF) was formulated using Cox coefficients to quantify the extent to which the performance of PHS46+African varies with PC.<h4>Results</h4>CF of PHS46+African was strongly associated with the first and twentieth PCs. Predicted CF ranged from 0.41 to 2.94, suggesting that PHS46+African may be up to 7 times more beneficial to some African men than others. The explained relative risk for PHS46+African varied from 3.6% to 9.9% for individuals with low and high CF values, respectively. By cross-referencing our data set with 1000 Genomes, we identified significant associations between continental and calibration groupings.<h4>Conclusion</h4>We identified PCs within 8q24 that were strongly associated with the performance of PHS46+African. Further research to improve the clinical utility of polygenic risk scores (or models) is needed to improve health outcomes for men of African ancestry.en_US
dc.formatPrint-Electronicen_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://www.rioxx.net/licenses/all-rights-reserveden_US
dc.subjectUKGPCS Collaboratorsen_US
dc.subjectPRACTICAL Consortiumen_US
dc.titlePerformance of African-ancestry-specific polygenic hazard score varies according to local ancestry in 8q24.en_US
dc.typeJournal Article
dcterms.dateAccepted2021-05-27
rioxxterms.versionAMen_US
rioxxterms.versionofrecord10.1038/s41391-021-00403-7en_US
rioxxterms.licenseref.startdate2021-06-14
dc.relation.isPartOfProstate cancer and prostatic diseasesen_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Oncogenetics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Radiotherapy and Imaging/Oncogenetics
pubs.publication-statusPublisheden_US
pubs.embargo.termsNot knownen_US
icr.researchteamOncogenetics
dc.contributor.icrauthorKote-Jarai, Zsofiaen_US
dc.contributor.icrauthorEeles, Rosalinden_US


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