| Title: | Testing the generalizability of ancestry-specific polygenic risk scores to predict prostate cancer in sub-Saharan Africa |
| Journal: | Genome Biology |
| Published: | 13 Sep 2022 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/36100952/ |
| DOI: | https://doi.org/10.1186/s13059-022-02766-z |
| URL: | https://genomebiology.biomedcentral.com/counter/pdf/10.1186/s13059-022-02766-z |
Publication 10464
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Abstract
BackgroundGenome-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.ResultsAllele 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.ConclusionsGenetic 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.</p>
48 Authors
- 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
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