PRState: Incorporating genetic ancestry in prostate cancer risk scores for men of African ancestry

Background Prostate cancer (PrCa) is one of the most genetically driven solid cancers with heritability estimates as high as 57%. Men of African ancestry are at an increased risk of PrCa; however, current polygenic risk score (PRS) models are based on European ancestry groups and may not be broadly...
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Autor*in:	Pagadala, Meghana S. [verfasserIn] Linscott, Joshua A. Talwar, James V. Seibert, Tyler M. Rose, Brent Lynch, Julie Panizzon, Matthew Hauger, Richard Hansen, Moritz H. Sammon, Jesse D. Hayn, Matthew H. Kader, Karim Carter, Hannah Ryan, Stephen T.

Format:	E-Artikel
Sprache:	Englisch

Erschienen:	2022

Schlagwörter:	Prostate Cancer Prostate Cancer Risk Single nucleotide polymorphism (SNP) Ancestry African Polygenic Risk Score (PRS)

Anmerkung:	© The Author(s) 2022

Übergeordnetes Werk:	Enthalten in: BMC cancer - London : BioMed Central, 2001, 22(2022), 1 vom: 09. Dez.
Übergeordnetes Werk:	volume:22 ; year:2022 ; number:1 ; day:09 ; month:12

Links:	Volltext

DOI / URN:	10.1186/s12885-022-10258-3

Katalog-ID:	SPR051218976

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520			\|a Background Prostate cancer (PrCa) is one of the most genetically driven solid cancers with heritability estimates as high as 57%. Men of African ancestry are at an increased risk of PrCa; however, current polygenic risk score (PRS) models are based on European ancestry groups and may not be broadly applicable. The objective of this study was to construct an African ancestry-specific PrCa PRS (PRState) and evaluate its performance. Methods African ancestry group of 4,533 individuals in ELLIPSE consortium was used for discovery of African ancestry-specific PrCa SNPs. PRState was constructed as weighted sum of genotypes and effect sizes from genome-wide association study (GWAS) of PrCa in African ancestry group. Performance was evaluated using ROC-AUC analysis. Results We identified African ancestry-specific PrCa risk loci on chromosomes 3, 8, and 11 and constructed a polygenic risk score (PRS) from 10 African ancestry-specific PrCa risk SNPs, achieving an AUC of 0.61 [0.60–0.63] and 0.65 [0.64–0.67], when combined with age and family history. Performance dropped significantly when using ancestry-mismatched PRS models but remained comparable when using trans-ancestry models. Importantly, we validated the PRState score in the Million Veteran Program (MVP), demonstrating improved prediction of PrCa and metastatic PrCa in individuals of African ancestry. Conclusions African ancestry-specific PRState improves PrCa prediction in African ancestry groups in ELLIPSE consortium and MVP. This study underscores the need for inclusion of individuals of African ancestry in gene variant discovery to optimize PRSs and identifies African ancestry-specific variants for use in future studies.
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allfields	10.1186/s12885-022-10258-3 doi (DE-627)SPR051218976 (SPR)s12885-022-10258-3-e DE-627 ger DE-627 rakwb eng Pagadala, Meghana S. verfasserin (orcid)0000-0002-7591-6035 aut PRState: Incorporating genetic ancestry in prostate cancer risk scores for men of African ancestry 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Prostate cancer (PrCa) is one of the most genetically driven solid cancers with heritability estimates as high as 57%. Men of African ancestry are at an increased risk of PrCa; however, current polygenic risk score (PRS) models are based on European ancestry groups and may not be broadly applicable. The objective of this study was to construct an African ancestry-specific PrCa PRS (PRState) and evaluate its performance. Methods African ancestry group of 4,533 individuals in ELLIPSE consortium was used for discovery of African ancestry-specific PrCa SNPs. PRState was constructed as weighted sum of genotypes and effect sizes from genome-wide association study (GWAS) of PrCa in African ancestry group. Performance was evaluated using ROC-AUC analysis. Results We identified African ancestry-specific PrCa risk loci on chromosomes 3, 8, and 11 and constructed a polygenic risk score (PRS) from 10 African ancestry-specific PrCa risk SNPs, achieving an AUC of 0.61 [0.60–0.63] and 0.65 [0.64–0.67], when combined with age and family history. Performance dropped significantly when using ancestry-mismatched PRS models but remained comparable when using trans-ancestry models. Importantly, we validated the PRState score in the Million Veteran Program (MVP), demonstrating improved prediction of PrCa and metastatic PrCa in individuals of African ancestry. Conclusions African ancestry-specific PRState improves PrCa prediction in African ancestry groups in ELLIPSE consortium and MVP. This study underscores the need for inclusion of individuals of African ancestry in gene variant discovery to optimize PRSs and identifies African ancestry-specific variants for use in future studies. Prostate Cancer (dpeaa)DE-He213 Prostate Cancer Risk (dpeaa)DE-He213 Single nucleotide polymorphism (SNP) (dpeaa)DE-He213 Ancestry (dpeaa)DE-He213 African (dpeaa)DE-He213 Polygenic Risk Score (PRS) (dpeaa)DE-He213 Linscott, Joshua A. aut Talwar, James V. aut Seibert, Tyler M. aut Rose, Brent aut Lynch, Julie aut Panizzon, Matthew aut Hauger, Richard aut Hansen, Moritz H. aut Sammon, Jesse D. aut Hayn, Matthew H. aut Kader, Karim aut Carter, Hannah aut Ryan, Stephen T. aut Enthalten in BMC cancer London : BioMed Central, 2001 22(2022), 1 vom: 09. Dez. (DE-627)326643710 (DE-600)2041352-X 1471-2407 nnns volume:22 year:2022 number:1 day:09 month:12 https://dx.doi.org/10.1186/s12885-022-10258-3 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2022 1 09 12
spelling	10.1186/s12885-022-10258-3 doi (DE-627)SPR051218976 (SPR)s12885-022-10258-3-e DE-627 ger DE-627 rakwb eng Pagadala, Meghana S. verfasserin (orcid)0000-0002-7591-6035 aut PRState: Incorporating genetic ancestry in prostate cancer risk scores for men of African ancestry 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Prostate cancer (PrCa) is one of the most genetically driven solid cancers with heritability estimates as high as 57%. Men of African ancestry are at an increased risk of PrCa; however, current polygenic risk score (PRS) models are based on European ancestry groups and may not be broadly applicable. The objective of this study was to construct an African ancestry-specific PrCa PRS (PRState) and evaluate its performance. Methods African ancestry group of 4,533 individuals in ELLIPSE consortium was used for discovery of African ancestry-specific PrCa SNPs. PRState was constructed as weighted sum of genotypes and effect sizes from genome-wide association study (GWAS) of PrCa in African ancestry group. Performance was evaluated using ROC-AUC analysis. Results We identified African ancestry-specific PrCa risk loci on chromosomes 3, 8, and 11 and constructed a polygenic risk score (PRS) from 10 African ancestry-specific PrCa risk SNPs, achieving an AUC of 0.61 [0.60–0.63] and 0.65 [0.64–0.67], when combined with age and family history. Performance dropped significantly when using ancestry-mismatched PRS models but remained comparable when using trans-ancestry models. Importantly, we validated the PRState score in the Million Veteran Program (MVP), demonstrating improved prediction of PrCa and metastatic PrCa in individuals of African ancestry. Conclusions African ancestry-specific PRState improves PrCa prediction in African ancestry groups in ELLIPSE consortium and MVP. This study underscores the need for inclusion of individuals of African ancestry in gene variant discovery to optimize PRSs and identifies African ancestry-specific variants for use in future studies. Prostate Cancer (dpeaa)DE-He213 Prostate Cancer Risk (dpeaa)DE-He213 Single nucleotide polymorphism (SNP) (dpeaa)DE-He213 Ancestry (dpeaa)DE-He213 African (dpeaa)DE-He213 Polygenic Risk Score (PRS) (dpeaa)DE-He213 Linscott, Joshua A. aut Talwar, James V. aut Seibert, Tyler M. aut Rose, Brent aut Lynch, Julie aut Panizzon, Matthew aut Hauger, Richard aut Hansen, Moritz H. aut Sammon, Jesse D. aut Hayn, Matthew H. aut Kader, Karim aut Carter, Hannah aut Ryan, Stephen T. aut Enthalten in BMC cancer London : BioMed Central, 2001 22(2022), 1 vom: 09. Dez. (DE-627)326643710 (DE-600)2041352-X 1471-2407 nnns volume:22 year:2022 number:1 day:09 month:12 https://dx.doi.org/10.1186/s12885-022-10258-3 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2022 1 09 12
allfields_unstemmed	10.1186/s12885-022-10258-3 doi (DE-627)SPR051218976 (SPR)s12885-022-10258-3-e DE-627 ger DE-627 rakwb eng Pagadala, Meghana S. verfasserin (orcid)0000-0002-7591-6035 aut PRState: Incorporating genetic ancestry in prostate cancer risk scores for men of African ancestry 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Prostate cancer (PrCa) is one of the most genetically driven solid cancers with heritability estimates as high as 57%. Men of African ancestry are at an increased risk of PrCa; however, current polygenic risk score (PRS) models are based on European ancestry groups and may not be broadly applicable. The objective of this study was to construct an African ancestry-specific PrCa PRS (PRState) and evaluate its performance. Methods African ancestry group of 4,533 individuals in ELLIPSE consortium was used for discovery of African ancestry-specific PrCa SNPs. PRState was constructed as weighted sum of genotypes and effect sizes from genome-wide association study (GWAS) of PrCa in African ancestry group. Performance was evaluated using ROC-AUC analysis. Results We identified African ancestry-specific PrCa risk loci on chromosomes 3, 8, and 11 and constructed a polygenic risk score (PRS) from 10 African ancestry-specific PrCa risk SNPs, achieving an AUC of 0.61 [0.60–0.63] and 0.65 [0.64–0.67], when combined with age and family history. Performance dropped significantly when using ancestry-mismatched PRS models but remained comparable when using trans-ancestry models. Importantly, we validated the PRState score in the Million Veteran Program (MVP), demonstrating improved prediction of PrCa and metastatic PrCa in individuals of African ancestry. Conclusions African ancestry-specific PRState improves PrCa prediction in African ancestry groups in ELLIPSE consortium and MVP. This study underscores the need for inclusion of individuals of African ancestry in gene variant discovery to optimize PRSs and identifies African ancestry-specific variants for use in future studies. Prostate Cancer (dpeaa)DE-He213 Prostate Cancer Risk (dpeaa)DE-He213 Single nucleotide polymorphism (SNP) (dpeaa)DE-He213 Ancestry (dpeaa)DE-He213 African (dpeaa)DE-He213 Polygenic Risk Score (PRS) (dpeaa)DE-He213 Linscott, Joshua A. aut Talwar, James V. aut Seibert, Tyler M. aut Rose, Brent aut Lynch, Julie aut Panizzon, Matthew aut Hauger, Richard aut Hansen, Moritz H. aut Sammon, Jesse D. aut Hayn, Matthew H. aut Kader, Karim aut Carter, Hannah aut Ryan, Stephen T. aut Enthalten in BMC cancer London : BioMed Central, 2001 22(2022), 1 vom: 09. Dez. (DE-627)326643710 (DE-600)2041352-X 1471-2407 nnns volume:22 year:2022 number:1 day:09 month:12 https://dx.doi.org/10.1186/s12885-022-10258-3 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2022 1 09 12
allfieldsGer	10.1186/s12885-022-10258-3 doi (DE-627)SPR051218976 (SPR)s12885-022-10258-3-e DE-627 ger DE-627 rakwb eng Pagadala, Meghana S. verfasserin (orcid)0000-0002-7591-6035 aut PRState: Incorporating genetic ancestry in prostate cancer risk scores for men of African ancestry 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Prostate cancer (PrCa) is one of the most genetically driven solid cancers with heritability estimates as high as 57%. Men of African ancestry are at an increased risk of PrCa; however, current polygenic risk score (PRS) models are based on European ancestry groups and may not be broadly applicable. The objective of this study was to construct an African ancestry-specific PrCa PRS (PRState) and evaluate its performance. Methods African ancestry group of 4,533 individuals in ELLIPSE consortium was used for discovery of African ancestry-specific PrCa SNPs. PRState was constructed as weighted sum of genotypes and effect sizes from genome-wide association study (GWAS) of PrCa in African ancestry group. Performance was evaluated using ROC-AUC analysis. Results We identified African ancestry-specific PrCa risk loci on chromosomes 3, 8, and 11 and constructed a polygenic risk score (PRS) from 10 African ancestry-specific PrCa risk SNPs, achieving an AUC of 0.61 [0.60–0.63] and 0.65 [0.64–0.67], when combined with age and family history. Performance dropped significantly when using ancestry-mismatched PRS models but remained comparable when using trans-ancestry models. Importantly, we validated the PRState score in the Million Veteran Program (MVP), demonstrating improved prediction of PrCa and metastatic PrCa in individuals of African ancestry. Conclusions African ancestry-specific PRState improves PrCa prediction in African ancestry groups in ELLIPSE consortium and MVP. This study underscores the need for inclusion of individuals of African ancestry in gene variant discovery to optimize PRSs and identifies African ancestry-specific variants for use in future studies. Prostate Cancer (dpeaa)DE-He213 Prostate Cancer Risk (dpeaa)DE-He213 Single nucleotide polymorphism (SNP) (dpeaa)DE-He213 Ancestry (dpeaa)DE-He213 African (dpeaa)DE-He213 Polygenic Risk Score (PRS) (dpeaa)DE-He213 Linscott, Joshua A. aut Talwar, James V. aut Seibert, Tyler M. aut Rose, Brent aut Lynch, Julie aut Panizzon, Matthew aut Hauger, Richard aut Hansen, Moritz H. aut Sammon, Jesse D. aut Hayn, Matthew H. aut Kader, Karim aut Carter, Hannah aut Ryan, Stephen T. aut Enthalten in BMC cancer London : BioMed Central, 2001 22(2022), 1 vom: 09. Dez. (DE-627)326643710 (DE-600)2041352-X 1471-2407 nnns volume:22 year:2022 number:1 day:09 month:12 https://dx.doi.org/10.1186/s12885-022-10258-3 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2022 1 09 12
allfieldsSound	10.1186/s12885-022-10258-3 doi (DE-627)SPR051218976 (SPR)s12885-022-10258-3-e DE-627 ger DE-627 rakwb eng Pagadala, Meghana S. verfasserin (orcid)0000-0002-7591-6035 aut PRState: Incorporating genetic ancestry in prostate cancer risk scores for men of African ancestry 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier © The Author(s) 2022 Background Prostate cancer (PrCa) is one of the most genetically driven solid cancers with heritability estimates as high as 57%. Men of African ancestry are at an increased risk of PrCa; however, current polygenic risk score (PRS) models are based on European ancestry groups and may not be broadly applicable. The objective of this study was to construct an African ancestry-specific PrCa PRS (PRState) and evaluate its performance. Methods African ancestry group of 4,533 individuals in ELLIPSE consortium was used for discovery of African ancestry-specific PrCa SNPs. PRState was constructed as weighted sum of genotypes and effect sizes from genome-wide association study (GWAS) of PrCa in African ancestry group. Performance was evaluated using ROC-AUC analysis. Results We identified African ancestry-specific PrCa risk loci on chromosomes 3, 8, and 11 and constructed a polygenic risk score (PRS) from 10 African ancestry-specific PrCa risk SNPs, achieving an AUC of 0.61 [0.60–0.63] and 0.65 [0.64–0.67], when combined with age and family history. Performance dropped significantly when using ancestry-mismatched PRS models but remained comparable when using trans-ancestry models. Importantly, we validated the PRState score in the Million Veteran Program (MVP), demonstrating improved prediction of PrCa and metastatic PrCa in individuals of African ancestry. Conclusions African ancestry-specific PRState improves PrCa prediction in African ancestry groups in ELLIPSE consortium and MVP. This study underscores the need for inclusion of individuals of African ancestry in gene variant discovery to optimize PRSs and identifies African ancestry-specific variants for use in future studies. Prostate Cancer (dpeaa)DE-He213 Prostate Cancer Risk (dpeaa)DE-He213 Single nucleotide polymorphism (SNP) (dpeaa)DE-He213 Ancestry (dpeaa)DE-He213 African (dpeaa)DE-He213 Polygenic Risk Score (PRS) (dpeaa)DE-He213 Linscott, Joshua A. aut Talwar, James V. aut Seibert, Tyler M. aut Rose, Brent aut Lynch, Julie aut Panizzon, Matthew aut Hauger, Richard aut Hansen, Moritz H. aut Sammon, Jesse D. aut Hayn, Matthew H. aut Kader, Karim aut Carter, Hannah aut Ryan, Stephen T. aut Enthalten in BMC cancer London : BioMed Central, 2001 22(2022), 1 vom: 09. Dez. (DE-627)326643710 (DE-600)2041352-X 1471-2407 nnns volume:22 year:2022 number:1 day:09 month:12 https://dx.doi.org/10.1186/s12885-022-10258-3 kostenfrei Volltext GBV_USEFLAG_A SYSFLAG_A GBV_SPRINGER GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2031 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2057 GBV_ILN_2061 GBV_ILN_2111 GBV_ILN_2113 GBV_ILN_2190 GBV_ILN_4012 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4249 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4700 AR 22 2022 1 09 12
language	English
source	Enthalten in BMC cancer 22(2022), 1 vom: 09. Dez. volume:22 year:2022 number:1 day:09 month:12
sourceStr	Enthalten in BMC cancer 22(2022), 1 vom: 09. Dez. volume:22 year:2022 number:1 day:09 month:12
format_phy_str_mv	Article
institution	findex.gbv.de
topic_facet	Prostate Cancer Prostate Cancer Risk Single nucleotide polymorphism (SNP) Ancestry African Polygenic Risk Score (PRS)
isfreeaccess_bool	true
container_title	BMC cancer
authorswithroles_txt_mv	Pagadala, Meghana S. @@aut@@ Linscott, Joshua A. @@aut@@ Talwar, James V. @@aut@@ Seibert, Tyler M. @@aut@@ Rose, Brent @@aut@@ Lynch, Julie @@aut@@ Panizzon, Matthew @@aut@@ Hauger, Richard @@aut@@ Hansen, Moritz H. @@aut@@ Sammon, Jesse D. @@aut@@ Hayn, Matthew H. @@aut@@ Kader, Karim @@aut@@ Carter, Hannah @@aut@@ Ryan, Stephen T. @@aut@@
publishDateDaySort_date	2022-12-09T00:00:00Z
hierarchy_top_id	326643710
id	SPR051218976
language_de	englisch
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Men of African ancestry are at an increased risk of PrCa; however, current polygenic risk score (PRS) models are based on European ancestry groups and may not be broadly applicable. The objective of this study was to construct an African ancestry-specific PrCa PRS (PRState) and evaluate its performance. Methods African ancestry group of 4,533 individuals in ELLIPSE consortium was used for discovery of African ancestry-specific PrCa SNPs. PRState was constructed as weighted sum of genotypes and effect sizes from genome-wide association study (GWAS) of PrCa in African ancestry group. Performance was evaluated using ROC-AUC analysis. Results We identified African ancestry-specific PrCa risk loci on chromosomes 3, 8, and 11 and constructed a polygenic risk score (PRS) from 10 African ancestry-specific PrCa risk SNPs, achieving an AUC of 0.61 [0.60–0.63] and 0.65 [0.64–0.67], when combined with age and family history. Performance dropped significantly when using ancestry-mismatched PRS models but remained comparable when using trans-ancestry models. Importantly, we validated the PRState score in the Million Veteran Program (MVP), demonstrating improved prediction of PrCa and metastatic PrCa in individuals of African ancestry. Conclusions African ancestry-specific PRState improves PrCa prediction in African ancestry groups in ELLIPSE consortium and MVP. 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author	Pagadala, Meghana S.
spellingShingle	Pagadala, Meghana S. misc Prostate Cancer misc Prostate Cancer Risk misc Single nucleotide polymorphism (SNP) misc Ancestry misc African misc Polygenic Risk Score (PRS) PRState: Incorporating genetic ancestry in prostate cancer risk scores for men of African ancestry
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topic_title	PRState: Incorporating genetic ancestry in prostate cancer risk scores for men of African ancestry Prostate Cancer (dpeaa)DE-He213 Prostate Cancer Risk (dpeaa)DE-He213 Single nucleotide polymorphism (SNP) (dpeaa)DE-He213 Ancestry (dpeaa)DE-He213 African (dpeaa)DE-He213 Polygenic Risk Score (PRS) (dpeaa)DE-He213
topic	misc Prostate Cancer misc Prostate Cancer Risk misc Single nucleotide polymorphism (SNP) misc Ancestry misc African misc Polygenic Risk Score (PRS)
topic_unstemmed	misc Prostate Cancer misc Prostate Cancer Risk misc Single nucleotide polymorphism (SNP) misc Ancestry misc African misc Polygenic Risk Score (PRS)
topic_browse	misc Prostate Cancer misc Prostate Cancer Risk misc Single nucleotide polymorphism (SNP) misc Ancestry misc African misc Polygenic Risk Score (PRS)
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title	PRState: Incorporating genetic ancestry in prostate cancer risk scores for men of African ancestry
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title_full	PRState: Incorporating genetic ancestry in prostate cancer risk scores for men of African ancestry
author_sort	Pagadala, Meghana S.
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author_browse	Pagadala, Meghana S. Linscott, Joshua A. Talwar, James V. Seibert, Tyler M. Rose, Brent Lynch, Julie Panizzon, Matthew Hauger, Richard Hansen, Moritz H. Sammon, Jesse D. Hayn, Matthew H. Kader, Karim Carter, Hannah Ryan, Stephen T.
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author-letter	Pagadala, Meghana S.
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title_sort	prstate: incorporating genetic ancestry in prostate cancer risk scores for men of african ancestry
title_auth	PRState: Incorporating genetic ancestry in prostate cancer risk scores for men of African ancestry
abstract	Background Prostate cancer (PrCa) is one of the most genetically driven solid cancers with heritability estimates as high as 57%. Men of African ancestry are at an increased risk of PrCa; however, current polygenic risk score (PRS) models are based on European ancestry groups and may not be broadly applicable. The objective of this study was to construct an African ancestry-specific PrCa PRS (PRState) and evaluate its performance. Methods African ancestry group of 4,533 individuals in ELLIPSE consortium was used for discovery of African ancestry-specific PrCa SNPs. PRState was constructed as weighted sum of genotypes and effect sizes from genome-wide association study (GWAS) of PrCa in African ancestry group. Performance was evaluated using ROC-AUC analysis. Results We identified African ancestry-specific PrCa risk loci on chromosomes 3, 8, and 11 and constructed a polygenic risk score (PRS) from 10 African ancestry-specific PrCa risk SNPs, achieving an AUC of 0.61 [0.60–0.63] and 0.65 [0.64–0.67], when combined with age and family history. Performance dropped significantly when using ancestry-mismatched PRS models but remained comparable when using trans-ancestry models. Importantly, we validated the PRState score in the Million Veteran Program (MVP), demonstrating improved prediction of PrCa and metastatic PrCa in individuals of African ancestry. Conclusions African ancestry-specific PRState improves PrCa prediction in African ancestry groups in ELLIPSE consortium and MVP. This study underscores the need for inclusion of individuals of African ancestry in gene variant discovery to optimize PRSs and identifies African ancestry-specific variants for use in future studies. © The Author(s) 2022
abstractGer	Background Prostate cancer (PrCa) is one of the most genetically driven solid cancers with heritability estimates as high as 57%. Men of African ancestry are at an increased risk of PrCa; however, current polygenic risk score (PRS) models are based on European ancestry groups and may not be broadly applicable. The objective of this study was to construct an African ancestry-specific PrCa PRS (PRState) and evaluate its performance. Methods African ancestry group of 4,533 individuals in ELLIPSE consortium was used for discovery of African ancestry-specific PrCa SNPs. PRState was constructed as weighted sum of genotypes and effect sizes from genome-wide association study (GWAS) of PrCa in African ancestry group. Performance was evaluated using ROC-AUC analysis. Results We identified African ancestry-specific PrCa risk loci on chromosomes 3, 8, and 11 and constructed a polygenic risk score (PRS) from 10 African ancestry-specific PrCa risk SNPs, achieving an AUC of 0.61 [0.60–0.63] and 0.65 [0.64–0.67], when combined with age and family history. Performance dropped significantly when using ancestry-mismatched PRS models but remained comparable when using trans-ancestry models. Importantly, we validated the PRState score in the Million Veteran Program (MVP), demonstrating improved prediction of PrCa and metastatic PrCa in individuals of African ancestry. Conclusions African ancestry-specific PRState improves PrCa prediction in African ancestry groups in ELLIPSE consortium and MVP. This study underscores the need for inclusion of individuals of African ancestry in gene variant discovery to optimize PRSs and identifies African ancestry-specific variants for use in future studies. © The Author(s) 2022
abstract_unstemmed	Background Prostate cancer (PrCa) is one of the most genetically driven solid cancers with heritability estimates as high as 57%. Men of African ancestry are at an increased risk of PrCa; however, current polygenic risk score (PRS) models are based on European ancestry groups and may not be broadly applicable. The objective of this study was to construct an African ancestry-specific PrCa PRS (PRState) and evaluate its performance. Methods African ancestry group of 4,533 individuals in ELLIPSE consortium was used for discovery of African ancestry-specific PrCa SNPs. PRState was constructed as weighted sum of genotypes and effect sizes from genome-wide association study (GWAS) of PrCa in African ancestry group. Performance was evaluated using ROC-AUC analysis. Results We identified African ancestry-specific PrCa risk loci on chromosomes 3, 8, and 11 and constructed a polygenic risk score (PRS) from 10 African ancestry-specific PrCa risk SNPs, achieving an AUC of 0.61 [0.60–0.63] and 0.65 [0.64–0.67], when combined with age and family history. Performance dropped significantly when using ancestry-mismatched PRS models but remained comparable when using trans-ancestry models. Importantly, we validated the PRState score in the Million Veteran Program (MVP), demonstrating improved prediction of PrCa and metastatic PrCa in individuals of African ancestry. Conclusions African ancestry-specific PRState improves PrCa prediction in African ancestry groups in ELLIPSE consortium and MVP. This study underscores the need for inclusion of individuals of African ancestry in gene variant discovery to optimize PRSs and identifies African ancestry-specific variants for use in future studies. © The Author(s) 2022
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title_short	PRState: Incorporating genetic ancestry in prostate cancer risk scores for men of African ancestry
url	https://dx.doi.org/10.1186/s12885-022-10258-3
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author2	Linscott, Joshua A. Talwar, James V. Seibert, Tyler M. Rose, Brent Lynch, Julie Panizzon, Matthew Hauger, Richard Hansen, Moritz H. Sammon, Jesse D. Hayn, Matthew H. Kader, Karim Carter, Hannah Ryan, Stephen T.
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up_date	2024-07-03T20:29:49.989Z
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