Testing the generalizability of ancestry-specific polygenic risk scores to predict prostate cancer in sub-Saharan Africa
Abstract Background Genome-wide association studies do not always replicate well across populations, limiting the generalizability of polygenic risk scores (PRS). Despite higher incidence and mortality rates of prostate cancer in men of African descent, much of what is known about cancer genetics co...
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| Format: | Article |
| Language: | English |
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BMC
2022-09-01
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| Series: | Genome Biology |
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| Online Access: | https://doi.org/10.1186/s13059-022-02766-z |
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| author | Michelle S. Kim Daphne Naidoo Ujani Hazra Melanie H. Quiver Wenlong C. Chen Corinne N. Simonti Paidamoyo Kachambwa Maxine Harlemon Ilir Agalliu Shakuntala Baichoo Pedro Fernandez Ann W. Hsing Mohamed Jalloh Serigne M. Gueye Lamine Niang Halimatou Diop Medina Ndoye Nana Yaa Snyper Ben Adusei James E. Mensah Afua O. D. Abrahams Richard Biritwum Andrew A. Adjei Akindele O. Adebiyi Olayiwola Shittu Olufemi Ogunbiyi Sikiru Adebayo Oseremen I. Aisuodionoe-Shadrach Maxwell M. Nwegbu Hafees O. Ajibola Olabode P. Oluwole Mustapha A. Jamda Elvira Singh Audrey Pentz Maureen Joffe Burcu F. Darst David V. Conti Christopher A. Haiman Petrus V. Spies André van der Merwe Thomas E. Rohan Judith Jacobson Alfred I. Neugut Jo McBride Caroline Andrews Lindsay N. Petersen Timothy R. Rebbeck Joseph Lachance |
| author_facet | Michelle S. Kim Daphne Naidoo Ujani Hazra Melanie H. Quiver Wenlong C. Chen Corinne N. Simonti Paidamoyo Kachambwa Maxine Harlemon Ilir Agalliu Shakuntala Baichoo Pedro Fernandez Ann W. Hsing Mohamed Jalloh Serigne M. Gueye Lamine Niang Halimatou Diop Medina Ndoye Nana Yaa Snyper Ben Adusei James E. Mensah Afua O. D. Abrahams Richard Biritwum Andrew A. Adjei Akindele O. Adebiyi Olayiwola Shittu Olufemi Ogunbiyi Sikiru Adebayo Oseremen I. Aisuodionoe-Shadrach Maxwell M. Nwegbu Hafees O. Ajibola Olabode P. Oluwole Mustapha A. Jamda Elvira Singh Audrey Pentz Maureen Joffe Burcu F. Darst David V. Conti Christopher A. Haiman Petrus V. Spies André van der Merwe Thomas E. Rohan Judith Jacobson Alfred I. Neugut Jo McBride Caroline Andrews Lindsay N. Petersen Timothy R. Rebbeck Joseph Lachance |
| author_sort | Michelle S. Kim |
| collection | DOAJ |
| description | Abstract Background Genome-wide association studies do not always replicate well across populations, limiting the generalizability of polygenic risk scores (PRS). Despite higher incidence and mortality rates of prostate cancer in men of African descent, much of what is known about cancer genetics comes from populations of European descent. To understand how well genetic predictions perform in different populations, we evaluated test characteristics of PRS from three previous studies using data from the UK Biobank and a novel dataset of 1298 prostate cancer cases and 1333 controls from Ghana, Nigeria, Senegal, and South Africa. Results Allele frequency differences cause predicted risks of prostate cancer to vary across populations. However, natural selection is not the primary driver of these differences. Comparing continental datasets, we find that polygenic predictions of case vs. control status are more effective for European individuals (AUC 0.608–0.707, OR 2.37–5.71) than for African individuals (AUC 0.502–0.585, OR 0.95–2.01). Furthermore, PRS that leverage information from African Americans yield modest AUC and odds ratio improvements for sub-Saharan African individuals. These improvements were larger for West Africans than for South Africans. Finally, we find that existing PRS are largely unable to predict whether African individuals develop aggressive forms of prostate cancer, as specified by higher tumor stages or Gleason scores. Conclusions Genetic predictions of prostate cancer perform poorly if the study sample does not match the ancestry of the original GWAS. PRS built from European GWAS may be inadequate for application in non-European populations and perpetuate existing health disparities. |
| first_indexed | 2024-04-12T21:04:36Z |
| format | Article |
| id | doaj.art-2fb0ba33d74e488caec70d594a0a5e30 |
| institution | Directory Open Access Journal |
| issn | 1474-760X |
| language | English |
| last_indexed | 2024-04-12T21:04:36Z |
| publishDate | 2022-09-01 |
| publisher | BMC |
| record_format | Article |
| series | Genome Biology |
| spelling | doaj.art-2fb0ba33d74e488caec70d594a0a5e302022-12-22T03:16:45ZengBMCGenome Biology1474-760X2022-09-0123111610.1186/s13059-022-02766-zTesting the generalizability of ancestry-specific polygenic risk scores to predict prostate cancer in sub-Saharan AfricaMichelle S. Kim0Daphne Naidoo1Ujani Hazra2Melanie H. Quiver3Wenlong C. Chen4Corinne N. Simonti5Paidamoyo Kachambwa6Maxine Harlemon7Ilir Agalliu8Shakuntala Baichoo9Pedro Fernandez10Ann W. Hsing11Mohamed Jalloh12Serigne M. Gueye13Lamine Niang14Halimatou Diop15Medina Ndoye16Nana Yaa Snyper17Ben Adusei18James E. Mensah19Afua O. D. Abrahams20Richard Biritwum21Andrew A. Adjei22Akindele O. Adebiyi23Olayiwola Shittu24Olufemi Ogunbiyi25Sikiru Adebayo26Oseremen I. Aisuodionoe-Shadrach27Maxwell M. Nwegbu28Hafees O. Ajibola29Olabode P. Oluwole30Mustapha A. Jamda31Elvira Singh32Audrey Pentz33Maureen Joffe34Burcu F. Darst35David V. Conti36Christopher A. Haiman37Petrus V. Spies38André van der Merwe39Thomas E. Rohan40Judith Jacobson41Alfred I. Neugut42Jo McBride43Caroline Andrews44Lindsay N. Petersen45Timothy R. Rebbeck46Joseph Lachance47School of Biological Sciences, Georgia Institute of TechnologyCentre for Proteomic and Genomic ResearchSchool of Biological Sciences, Georgia Institute of TechnologySchool of Biological Sciences, Georgia Institute of TechnologySydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the WitwatersrandSchool of Biological Sciences, Georgia Institute of TechnologyCentre for Proteomic and Genomic ResearchSchool of Biological Sciences, Georgia Institute of TechnologyDepartment of Epidemiology and Population Health, Albert Einstein College of MedicineUniversity of MauritiusFaculty of Medicine and Health Sciences, Stellenbosch UniversityStanford Cancer Institute, Stanford UniversityUniversite Cheikh Anta Diop de DakarUniversite Cheikh Anta Diop de DakarUniversite Cheikh Anta Diop de DakarUniversite Cheikh Anta Diop de DakarUniversite Cheikh Anta Diop de Dakar37 Military Hospital37 Military HospitalKorle-Bu Teaching Hospital and University of Ghana Medical SchoolKorle-Bu Teaching Hospital and University of Ghana Medical SchoolKorle-Bu Teaching Hospital and University of Ghana Medical SchoolDepartment of Pathology, University of Ghana Medical SchoolCollege of Medicine, University of IbadanCollege of Medicine, University of IbadanCollege of Medicine, University of IbadanCollege of Medicine, University of IbadanCollege of Health Sciences, University of Abuja and University of Abuja Teaching HospitalCollege of Health Sciences, University of Abuja and University of Abuja Teaching HospitalCollege of Health Sciences, University of Abuja and University of Abuja Teaching HospitalCollege of Health Sciences, University of Abuja and University of Abuja Teaching HospitalCollege of Health Sciences, University of Abuja and University of Abuja Teaching HospitalNational Cancer Registry, National Health Laboratory ServiceNon-Communicable Diseases Research Division, Wits Health Consortium (PTY) LtdNon-Communicable Diseases Research Division, Wits Health Consortium (PTY) LtdKeck School of Medicine, University of Southern CaliforniaKeck School of Medicine, University of Southern CaliforniaKeck School of Medicine, University of Southern CaliforniaFaculty of Medicine and Health Sciences, Stellenbosch UniversityFaculty of Medicine and Health Sciences, Stellenbosch UniversityDepartment of Epidemiology and Population Health, Albert Einstein College of MedicineHerbert Irving Comprehensive Cancer Center, Columbia UniversityHerbert Irving Comprehensive Cancer Center, Columbia UniversityCentre for Proteomic and Genomic ResearchDana-Farber Cancer InstituteCentre for Proteomic and Genomic ResearchDana-Farber Cancer InstituteSchool of Biological Sciences, Georgia Institute of TechnologyAbstract Background Genome-wide association studies do not always replicate well across populations, limiting the generalizability of polygenic risk scores (PRS). Despite higher incidence and mortality rates of prostate cancer in men of African descent, much of what is known about cancer genetics comes from populations of European descent. To understand how well genetic predictions perform in different populations, we evaluated test characteristics of PRS from three previous studies using data from the UK Biobank and a novel dataset of 1298 prostate cancer cases and 1333 controls from Ghana, Nigeria, Senegal, and South Africa. Results Allele frequency differences cause predicted risks of prostate cancer to vary across populations. However, natural selection is not the primary driver of these differences. Comparing continental datasets, we find that polygenic predictions of case vs. control status are more effective for European individuals (AUC 0.608–0.707, OR 2.37–5.71) than for African individuals (AUC 0.502–0.585, OR 0.95–2.01). Furthermore, PRS that leverage information from African Americans yield modest AUC and odds ratio improvements for sub-Saharan African individuals. These improvements were larger for West Africans than for South Africans. Finally, we find that existing PRS are largely unable to predict whether African individuals develop aggressive forms of prostate cancer, as specified by higher tumor stages or Gleason scores. Conclusions Genetic predictions of prostate cancer perform poorly if the study sample does not match the ancestry of the original GWAS. PRS built from European GWAS may be inadequate for application in non-European populations and perpetuate existing health disparities.https://doi.org/10.1186/s13059-022-02766-zAfricaHealth disparitiesGenomic medicinePolygenic risk scoresPopulation geneticsProstate cancer |
| spellingShingle | Michelle S. Kim Daphne Naidoo Ujani Hazra Melanie H. Quiver Wenlong C. Chen Corinne N. Simonti Paidamoyo Kachambwa Maxine Harlemon Ilir Agalliu Shakuntala Baichoo Pedro Fernandez Ann W. Hsing Mohamed Jalloh Serigne M. Gueye Lamine Niang Halimatou Diop Medina Ndoye Nana Yaa Snyper Ben Adusei James E. Mensah Afua O. D. Abrahams Richard Biritwum Andrew A. Adjei Akindele O. Adebiyi Olayiwola Shittu Olufemi Ogunbiyi Sikiru Adebayo Oseremen I. Aisuodionoe-Shadrach Maxwell M. Nwegbu Hafees O. Ajibola Olabode P. Oluwole Mustapha A. Jamda Elvira Singh Audrey Pentz Maureen Joffe Burcu F. Darst David V. Conti Christopher A. Haiman Petrus V. Spies André van der Merwe Thomas E. Rohan Judith Jacobson Alfred I. Neugut Jo McBride Caroline Andrews Lindsay N. Petersen Timothy R. Rebbeck Joseph Lachance Testing the generalizability of ancestry-specific polygenic risk scores to predict prostate cancer in sub-Saharan Africa Genome Biology Africa Health disparities Genomic medicine Polygenic risk scores Population genetics Prostate cancer |
| title | Testing the generalizability of ancestry-specific polygenic risk scores to predict prostate cancer in sub-Saharan Africa |
| title_full | Testing the generalizability of ancestry-specific polygenic risk scores to predict prostate cancer in sub-Saharan Africa |
| title_fullStr | Testing the generalizability of ancestry-specific polygenic risk scores to predict prostate cancer in sub-Saharan Africa |
| title_full_unstemmed | Testing the generalizability of ancestry-specific polygenic risk scores to predict prostate cancer in sub-Saharan Africa |
| title_short | Testing the generalizability of ancestry-specific polygenic risk scores to predict prostate cancer in sub-Saharan Africa |
| title_sort | testing the generalizability of ancestry specific polygenic risk scores to predict prostate cancer in sub saharan africa |
| topic | Africa Health disparities Genomic medicine Polygenic risk scores Population genetics Prostate cancer |
| url | https://doi.org/10.1186/s13059-022-02766-z |
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