"Performance of African-ancestry-specific polygenic hazard score varies" by Roshan A. Karunamuni, Minh-Phuong Huynh-Le et al.

Faculty Publications

Title

Performance of African-ancestry-specific polygenic hazard score varies according to local ancestry in 8q24

Authors

Roshan A. Karunamuni, Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA. rakarunamuni@health.ucsd.edu.
Minh-Phuong Huynh-Le, Radiation Oncology, George Washington University, Washington, DC, USA.
Chun C. Fan, Center for Human Development, University of California San Diego, La Jolla, CA, USA.
Wesley Thompson, Department of Family Medicine and Public Health, University of California, San Diego, La Jolla, CA, USA.
Asona Lui, Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA.
Maria Elena Martinez, Herbert Wertheim School of Public Health and Human Longevity Science, University of California San Diego, La Jolla, CA, USA.
Brent S. Rose, Department of Radiation Medicine and Applied Sciences, University of California San Diego, La Jolla, CA, USA.
Brandon Mahal, Department of Radiation Oncology, University of Miami Miller School of Medicine, Miami, FL, USA.
Rosalind A. Eeles, The Institute of Cancer Research, London, UK.
Zsofia Kote-Jarai, The Institute of Cancer Research, London, UK.
Kenneth Muir, Division of Population Health, Health Services Research and Primary Care, University of Manchester, Manchester, UK.
Artitaya Lophatananon, Division of Population Health, Health Services Research and Primary Care, University of Manchester, Manchester, UK.

Document Type

Article

Publication Date

2-1-2022

Abstract

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 Source (Journal or Book title)

Prostate cancer and prostatic diseases

First Page

229

Last Page

237

Recommended Citation

Karunamuni, R. A., Huynh-Le, M., Fan, C. C., Thompson, W., Lui, A., Martinez, M. E., Rose, B. S., Mahal, B., Eeles, R. A., Kote-Jarai, Z., Muir, K., & Lophatananon, A. (2022). Performance of African-ancestry-specific polygenic hazard score varies according to local ancestry in 8q24. Prostate cancer and prostatic diseases, 25 (2), 229-237. https://doi.org/10.1038/s41391-021-00403-7

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