Journal article
Performance of African-ancestry-specific polygenic hazard score varies according to local ancestry in 8q24
- Abstract:
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Background
We previously developed an African-ancestry-specific polygenic hazard score (PHS46+African) that substantially improved prostate cancer risk stratification in men with African ancestry. The model consists of 46 SNPs identified in Europeans and 3 SNPs from 8q24 shown to improve model performance in Africans. Herein, we used principal component (PC) analysis to uncover subpopulations of men with African ancestry for whom the utility of PHS46+African may differ.Materials and methods
Genotypic data were obtained from the PRACTICAL consortium for 6253 men with African genetic ancestry. Genetic variation in a window spanning 3 African-specific 8q24 SNPs was estimated using 93 PCs. A Cox proportional hazards framework was used to identify the pair of PCs most strongly associated with the performance of PHS46+African. A calibration factor (CF) was formulated using Cox coefficients to quantify the extent to which the performance of PHS46+African varies with PC.Results
CF of PHS46+African was strongly associated with the first and twentieth PCs. Predicted CF ranged from 0.41 to 2.94, suggesting that PHS46+African may be up to 7 times more beneficial to some African men than others. The explained relative risk for PHS46+African varied from 3.6% to 9.9% for individuals with low and high CF values, respectively. By cross-referencing our data set with 1000 Genomes, we identified significant associations between continental and calibration groupings.Conclusion
We identified PCs within 8q24 that were strongly associated with the performance of PHS46+African. Further research to improve the clinical utility of polygenic risk scores (or models) is needed to improve health outcomes for men of African ancestry.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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- Files:
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(Preview, Accepted manuscript, pdf, 283.4KB, Terms of use)
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- Publisher copy:
- 10.1038/s41391-021-00403-7
Authors
- Publisher:
- Springer Nature
- Journal:
- Prostate Cancer and Prostatic Diseases More from this journal
- Volume:
- 25
- Issue:
- 2
- Pages:
- 229–237
- Publication date:
- 2021-06-14
- Acceptance date:
- 2021-05-27
- DOI:
- EISSN:
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1476-5608
- ISSN:
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1365-7852
- Pmid:
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34127801
- Language:
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English
- Keywords:
- Pubs id:
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1182555
- Local pid:
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pubs:1182555
- Deposit date:
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2021-06-18
- ARK identifier:
Terms of use
- Copyright holder:
- Karunamuni et al.
- Copyright date:
- 2021
- Rights statement:
- © The Author(s), under exclusive licence to Springer Nature Limited 2021.
- Notes:
- This is the accepted manuscript version of the article. The final version is available online from Springer Nature at: https://doi.org/10.1038/s41391-021-00403-7
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