Testing the generalizability of ancestry-specific polygenic risk scores to predict prostate cancer in sub-Saharan Africa.

Autor: Kim MS; School of Biological Sciences, Georgia Institute of Technology, 950 Atlantic Dr, Atlanta, GA, 30332, USA., Naidoo D; Centre for Proteomic and Genomic Research, Cape Town, South Africa., Hazra U; School of Biological Sciences, Georgia Institute of Technology, 950 Atlantic Dr, Atlanta, GA, 30332, USA., Quiver MH; School of Biological Sciences, Georgia Institute of Technology, 950 Atlantic Dr, Atlanta, GA, 30332, USA., Chen WC; Sydney Brenner Institute for Molecular Bioscience, Faculty of Health Sciences, University of the Witwatersrand, Johannesburg, South Africa.; National Cancer Registry, National Health Laboratory Service, Johannesburg, South Africa., Simonti CN; School of Biological Sciences, Georgia Institute of Technology, 950 Atlantic Dr, Atlanta, GA, 30332, USA., Kachambwa P; Centre for Proteomic and Genomic Research, Cape Town, South Africa., Harlemon M; School of Biological Sciences, Georgia Institute of Technology, 950 Atlantic Dr, Atlanta, GA, 30332, USA., Agalliu I; Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA., Baichoo S; University of Mauritius, Réduit, Mauritius., Fernandez P; Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa., Hsing AW; Stanford Cancer Institute, Stanford University, Stanford, CA, USA., Jalloh M; Universite Cheikh Anta Diop de Dakar, Dakar, Senegal., Gueye SM; Universite Cheikh Anta Diop de Dakar, Dakar, Senegal., Niang L; Universite Cheikh Anta Diop de Dakar, Dakar, Senegal., Diop H; Universite Cheikh Anta Diop de Dakar, Dakar, Senegal., Ndoye M; Universite Cheikh Anta Diop de Dakar, Dakar, Senegal., Snyper NY; 37 Military Hospital, Accra, Ghana., Adusei B; 37 Military Hospital, Accra, Ghana., Mensah JE; Korle-Bu Teaching Hospital and University of Ghana Medical School, Accra, Ghana., Abrahams AOD; Korle-Bu Teaching Hospital and University of Ghana Medical School, Accra, Ghana., Biritwum R; Korle-Bu Teaching Hospital and University of Ghana Medical School, Accra, Ghana., Adjei AA; Department of Pathology, University of Ghana Medical School, Accra, Ghana., Adebiyi AO; College of Medicine, University of Ibadan, Ibadan, Nigeria., Shittu O; College of Medicine, University of Ibadan, Ibadan, Nigeria., Ogunbiyi O; College of Medicine, University of Ibadan, Ibadan, Nigeria., Adebayo S; College of Medicine, University of Ibadan, Ibadan, Nigeria., Aisuodionoe-Shadrach OI; College of Health Sciences, University of Abuja and University of Abuja Teaching Hospital, Abuja, Nigeria., Nwegbu MM; College of Health Sciences, University of Abuja and University of Abuja Teaching Hospital, Abuja, Nigeria., Ajibola HO; College of Health Sciences, University of Abuja and University of Abuja Teaching Hospital, Abuja, Nigeria., Oluwole OP; College of Health Sciences, University of Abuja and University of Abuja Teaching Hospital, Abuja, Nigeria., Jamda MA; College of Health Sciences, University of Abuja and University of Abuja Teaching Hospital, Abuja, Nigeria., Singh E; National Cancer Registry, National Health Laboratory Service, Johannesburg, South Africa., Pentz A; Non-Communicable Diseases Research Division, Wits Health Consortium (PTY) Ltd, Johannesburg, South Africa., Joffe M; Non-Communicable Diseases Research Division, Wits Health Consortium (PTY) Ltd, Johannesburg, South Africa.; MRC Developmental Pathways to Health Research Unit, Department of Pediatrics, Faculty of Health Sciences, University of Witwatersrand, Johannesburg, South Africa., Darst BF; Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Conti DV; Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Haiman CA; Keck School of Medicine, University of Southern California, Los Angeles, CA, USA., Spies PV; Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa., van der Merwe A; Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa., Rohan TE; Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, USA., Jacobson J; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA., Neugut AI; Herbert Irving Comprehensive Cancer Center, Columbia University, New York, NY, USA., McBride J; Centre for Proteomic and Genomic Research, Cape Town, South Africa., Andrews C; Dana-Farber Cancer Institute, Boston, MA, USA., Petersen LN; Centre for Proteomic and Genomic Research, Cape Town, South Africa., Rebbeck TR; Dana-Farber Cancer Institute, Boston, MA, USA.; Harvard T.H. Chan School of Public Health, Boston, MA, USA., Lachance J; School of Biological Sciences, Georgia Institute of Technology, 950 Atlantic Dr, Atlanta, GA, 30332, USA. joseph.lachance@biology.gatech.edu.
Jazyk: angličtina
Zdroj: Genome biology [Genome Biol] 2022 Sep 13; Vol. 23 (1), pp. 194. Date of Electronic Publication: 2022 Sep 13.
DOI: 10.1186/s13059-022-02766-z
Abstrakt: 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.
(© 2022. The Author(s).)
Databáze: MEDLINE
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