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Article: Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers

TitleAssessment of polygenic architecture and risk prediction based on common variants across fourteen cancers
Authors
Zhang, YHurson, AZhang, HChoudhury, PEaston, DMilne, RSimard, JHall, PMichailidou, KDennis, JSchmidt, MEeles, RHaiman, CKote-Jarai, ZSchumacher, FAl Olama, APurdue, MScelo, GDalgaard, MGreene, MGruber, SCasey, GGrotmol, TKanetsky, PMcGlynn, KNathanson, KTurnbull, CWiklund, FChanock, SChatterjee, NGarcia-Closas, MCasey, GSchmit, SSchmit, SO’Mara, TSpurdle, AThompson, DTomlinson, IDe Vivo,, ILandi, MLaw, MIles, MDemenais, FCampbel, PKumar, RMacGregor, SBishop, DWard, SBondy, MHoulston, RWiencke, JMelin, BBarnholtz-Sloan, JKinnersley, BHoffmeister, MWrensch, MAmos, CHung, RBrennan, PMcKay, JCaporaso, NBerndt, SBirmann, BCamp, NKraft, PJenkins, MRothman, NSlager, SBerchuck, APharoah, PSellers, TGayther, SPearce, CGoode, ESchildkraut, JMoysich, KPeters, UAmundadottir, LJacobs, EKlein, APetersen, GRisch, HStolzenberg-Solomon, RWolpin, BLi, DEeles, RHaiman, CHsu, LKote-Jarai, ZSchumacher, FAl Olama, APurdue, MScelo, GDalgaard, MGreene, MGrotmol, TKanetsky, PMcGlynn, KGruber, SNathanson, KTurnbull, CWiklund, FEaston,, DMilne, RSimard, JHall, PMichailidou, KDennis, JSchmidt, MCasey, GChang-Claude, JGharahkhani, PWhiteman, DCampbell, PHoffmeister, MJenkins, MPeters, UHsu, LGruber, SSchmit, SChang-Claude, JO’Mara, TSpurdle, AThompson, DTomlinson, IDe Vivo, ICampbell, PHoffmeister, MJenkins, MPeters, UHsu, LGharahkhani, PGruber, SCasey, GSchmit, SLandi, MLaw, MIles, MDemenais, FKumar, RMacGregor, SBishop, DWhiteman, DWard, SBondy, MHoulston, RWiencke, JMelin, BBarnholtz-Sloan, JKinnersley, BWrensch, MAmos, CHung, RCampbell, PBrennan, PMcKay, JCaporaso, NAmos, CHung, RBrennan, PMcKay, JCaporaso, NBerndt, SBirmann, BHoffmeister, MCamp, NKraft, PRothman, NSlager, SBerchuck, APharoah, PSellers, TGayther, SPearce, CGoode, EJenkins, MSchildkraut, JMoysich, KAmos, CBrennan, PMcKay, JAmundadottir, LJacobs, EKlein, APetersen, GRisch, HPeters, UStolzenberg-Solomon, RWolpin, BLi, DAmundadottir, LJacobs, EKlein, APetersen, GRisch, HStolzenberg-Solomon, RWolpin, BHsu, LLi,, D
Issue Date2020
PublisherNature Research: Fully open access journals. The Journal's web site is located at http://www.nature.com/ncomms/index.html
Citation
Nature Communications, 2020, v. 11 n. 1, p. article no. 3353 How to Cite?
AbstractGenome-wide association studies (GWAS) have led to the identification of hundreds of susceptibility loci across cancers, but the impact of further studies remains uncertain. Here we analyse summary-level data from GWAS of European ancestry across fourteen cancer sites to estimate the number of common susceptibility variants (polygenicity) and underlying effect-size distribution. All cancers show a high degree of polygenicity, involving at a minimum of thousands of loci. We project that sample sizes required to explain 80% of GWAS heritability vary from 60,000 cases for testicular to over 1,000,000 cases for lung cancer. The maximum relative risk achievable for subjects at the 99th risk percentile of underlying polygenic risk scores (PRS), compared to average risk, ranges from 12 for testicular to 2.5 for ovarian cancer. We show that PRS have potential for risk stratification for cancers of breast, colon and prostate, but less so for others because of modest heritability and lower incidence.
Persistent Identifierhttp://hdl.handle.net/10722/306169
ISSN
2023 Impact Factor: 14.7
2023 SCImago Journal Rankings: 4.887
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorZhang, Y-
dc.contributor.authorHurson, A-
dc.contributor.authorZhang, H-
dc.contributor.authorChoudhury, P-
dc.contributor.authorEaston, D-
dc.contributor.authorMilne, R-
dc.contributor.authorSimard, J-
dc.contributor.authorHall, P-
dc.contributor.authorMichailidou, K-
dc.contributor.authorDennis, J-
dc.contributor.authorSchmidt, M-
dc.contributor.authorEeles, R-
dc.contributor.authorHaiman, C-
dc.contributor.authorKote-Jarai, Z-
dc.contributor.authorSchumacher, F-
dc.contributor.authorAl Olama, A-
dc.contributor.authorPurdue, M-
dc.contributor.authorScelo, G-
dc.contributor.authorDalgaard, M-
dc.contributor.authorGreene, M-
dc.contributor.authorGruber, S-
dc.contributor.authorCasey, G-
dc.contributor.authorGrotmol, T-
dc.contributor.authorKanetsky, P-
dc.contributor.authorMcGlynn, K-
dc.contributor.authorNathanson, K-
dc.contributor.authorTurnbull, C-
dc.contributor.authorWiklund, F-
dc.contributor.authorChanock, S-
dc.contributor.authorChatterjee, N-
dc.contributor.authorGarcia-Closas, M-
dc.contributor.authorCasey, G-
dc.contributor.authorSchmit, S-
dc.contributor.authorSchmit, S-
dc.contributor.authorO’Mara, T-
dc.contributor.authorSpurdle, A-
dc.contributor.authorThompson, D-
dc.contributor.authorTomlinson, I-
dc.contributor.authorDe Vivo,, I-
dc.contributor.authorLandi, M-
dc.contributor.authorLaw, M-
dc.contributor.authorIles, M-
dc.contributor.authorDemenais, F-
dc.contributor.authorCampbel, P-
dc.contributor.authorKumar, R-
dc.contributor.authorMacGregor, S-
dc.contributor.authorBishop, D-
dc.contributor.authorWard, S-
dc.contributor.authorBondy, M-
dc.contributor.authorHoulston, R-
dc.contributor.authorWiencke, J-
dc.contributor.authorMelin, B-
dc.contributor.authorBarnholtz-Sloan, J-
dc.contributor.authorKinnersley, B-
dc.contributor.authorHoffmeister, M-
dc.contributor.authorWrensch, M-
dc.contributor.authorAmos, C-
dc.contributor.authorHung, R-
dc.contributor.authorBrennan, P-
dc.contributor.authorMcKay, J-
dc.contributor.authorCaporaso, N-
dc.contributor.authorBerndt, S-
dc.contributor.authorBirmann, B-
dc.contributor.authorCamp, N-
dc.contributor.authorKraft, P-
dc.contributor.authorJenkins, M-
dc.contributor.authorRothman, N-
dc.contributor.authorSlager, S-
dc.contributor.authorBerchuck, A-
dc.contributor.authorPharoah, P-
dc.contributor.authorSellers, T-
dc.contributor.authorGayther, S-
dc.contributor.authorPearce, C-
dc.contributor.authorGoode, E-
dc.contributor.authorSchildkraut, J-
dc.contributor.authorMoysich, K-
dc.contributor.authorPeters, U-
dc.contributor.authorAmundadottir, L-
dc.contributor.authorJacobs, E-
dc.contributor.authorKlein, A-
dc.contributor.authorPetersen, G-
dc.contributor.authorRisch, H-
dc.contributor.authorStolzenberg-Solomon, R-
dc.contributor.authorWolpin, B-
dc.contributor.authorLi, D-
dc.contributor.authorEeles, R-
dc.contributor.authorHaiman, C-
dc.contributor.authorHsu, L-
dc.contributor.authorKote-Jarai, Z-
dc.contributor.authorSchumacher, F-
dc.contributor.authorAl Olama, A-
dc.contributor.authorPurdue, M-
dc.contributor.authorScelo, G-
dc.contributor.authorDalgaard, M-
dc.contributor.authorGreene, M-
dc.contributor.authorGrotmol, T-
dc.contributor.authorKanetsky, P-
dc.contributor.authorMcGlynn, K-
dc.contributor.authorGruber, S-
dc.contributor.authorNathanson, K-
dc.contributor.authorTurnbull, C-
dc.contributor.authorWiklund, F-
dc.contributor.authorEaston,, D-
dc.contributor.authorMilne, R-
dc.contributor.authorSimard, J-
dc.contributor.authorHall, P-
dc.contributor.authorMichailidou, K-
dc.contributor.authorDennis, J-
dc.contributor.authorSchmidt, M-
dc.contributor.authorCasey, G-
dc.contributor.authorChang-Claude, J-
dc.contributor.authorGharahkhani, P-
dc.contributor.authorWhiteman, D-
dc.contributor.authorCampbell, P-
dc.contributor.authorHoffmeister, M-
dc.contributor.authorJenkins, M-
dc.contributor.authorPeters, U-
dc.contributor.authorHsu, L-
dc.contributor.authorGruber, S-
dc.contributor.authorSchmit, S-
dc.contributor.authorChang-Claude, J-
dc.contributor.authorO’Mara, T-
dc.contributor.authorSpurdle, A-
dc.contributor.authorThompson, D-
dc.contributor.authorTomlinson, I-
dc.contributor.authorDe Vivo, I-
dc.contributor.authorCampbell, P-
dc.contributor.authorHoffmeister, M-
dc.contributor.authorJenkins, M-
dc.contributor.authorPeters, U-
dc.contributor.authorHsu, L-
dc.contributor.authorGharahkhani, P-
dc.contributor.authorGruber, S-
dc.contributor.authorCasey, G-
dc.contributor.authorSchmit, S-
dc.contributor.authorLandi, M-
dc.contributor.authorLaw, M-
dc.contributor.authorIles, M-
dc.contributor.authorDemenais, F-
dc.contributor.authorKumar, R-
dc.contributor.authorMacGregor, S-
dc.contributor.authorBishop, D-
dc.contributor.authorWhiteman, D-
dc.contributor.authorWard, S-
dc.contributor.authorBondy, M-
dc.contributor.authorHoulston, R-
dc.contributor.authorWiencke, J-
dc.contributor.authorMelin, B-
dc.contributor.authorBarnholtz-Sloan, J-
dc.contributor.authorKinnersley, B-
dc.contributor.authorWrensch, M-
dc.contributor.authorAmos, C-
dc.contributor.authorHung, R-
dc.contributor.authorCampbell, P-
dc.contributor.authorBrennan, P-
dc.contributor.authorMcKay, J-
dc.contributor.authorCaporaso, N-
dc.contributor.authorAmos, C-
dc.contributor.authorHung, R-
dc.contributor.authorBrennan, P-
dc.contributor.authorMcKay, J-
dc.contributor.authorCaporaso, N-
dc.contributor.authorBerndt, S-
dc.contributor.authorBirmann, B-
dc.contributor.authorHoffmeister, M-
dc.contributor.authorCamp, N-
dc.contributor.authorKraft, P-
dc.contributor.authorRothman, N-
dc.contributor.authorSlager, S-
dc.contributor.authorBerchuck, A-
dc.contributor.authorPharoah, P-
dc.contributor.authorSellers, T-
dc.contributor.authorGayther, S-
dc.contributor.authorPearce, C-
dc.contributor.authorGoode, E-
dc.contributor.authorJenkins, M-
dc.contributor.authorSchildkraut, J-
dc.contributor.authorMoysich, K-
dc.contributor.authorAmos, C-
dc.contributor.authorBrennan, P-
dc.contributor.authorMcKay, J-
dc.contributor.authorAmundadottir, L-
dc.contributor.authorJacobs, E-
dc.contributor.authorKlein, A-
dc.contributor.authorPetersen, G-
dc.contributor.authorRisch, H-
dc.contributor.authorPeters, U-
dc.contributor.authorStolzenberg-Solomon, R-
dc.contributor.authorWolpin, B-
dc.contributor.authorLi, D-
dc.contributor.authorAmundadottir, L-
dc.contributor.authorJacobs, E-
dc.contributor.authorKlein, A-
dc.contributor.authorPetersen, G-
dc.contributor.authorRisch, H-
dc.contributor.authorStolzenberg-Solomon, R-
dc.contributor.authorWolpin, B-
dc.contributor.authorHsu, L-
dc.contributor.authorLi,, D-
dc.date.accessioned2021-10-20T10:19:46Z-
dc.date.available2021-10-20T10:19:46Z-
dc.date.issued2020-
dc.identifier.citationNature Communications, 2020, v. 11 n. 1, p. article no. 3353-
dc.identifier.issn2041-1723-
dc.identifier.urihttp://hdl.handle.net/10722/306169-
dc.description.abstractGenome-wide association studies (GWAS) have led to the identification of hundreds of susceptibility loci across cancers, but the impact of further studies remains uncertain. Here we analyse summary-level data from GWAS of European ancestry across fourteen cancer sites to estimate the number of common susceptibility variants (polygenicity) and underlying effect-size distribution. All cancers show a high degree of polygenicity, involving at a minimum of thousands of loci. We project that sample sizes required to explain 80% of GWAS heritability vary from 60,000 cases for testicular to over 1,000,000 cases for lung cancer. The maximum relative risk achievable for subjects at the 99th risk percentile of underlying polygenic risk scores (PRS), compared to average risk, ranges from 12 for testicular to 2.5 for ovarian cancer. We show that PRS have potential for risk stratification for cancers of breast, colon and prostate, but less so for others because of modest heritability and lower incidence.-
dc.languageeng-
dc.publisherNature Research: Fully open access journals. The Journal's web site is located at http://www.nature.com/ncomms/index.html-
dc.relation.ispartofNature Communications-
dc.rightsNature Communications. Copyright © Nature Research: Fully open access journals.-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.titleAssessment of polygenic architecture and risk prediction based on common variants across fourteen cancers-
dc.typeArticle-
dc.identifier.emailZhang, Y: doraz@hku.hk-
dc.identifier.authorityZhang, Y=rp02590-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1038/s41467-020-16483-3-
dc.identifier.pmid32620889-
dc.identifier.pmcidPMC7335068-
dc.identifier.scopuseid_2-s2.0-85087397990-
dc.identifier.hkuros327563-
dc.identifier.volume11-
dc.identifier.issue1-
dc.identifier.spagearticle no. 3353-
dc.identifier.epagearticle no. 3353-
dc.identifier.isiWOS:000546623500053-
dc.publisher.placeUnited Kingdom-

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