Performance of African-ancestry-specific polygenic hazard score varies according to local ancestry in 8q24 - Université des Antilles Access content directly
Journal Articles Prostate Cancer and Prostatic Diseases Year : 2021

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

Wesley Thompson
  • Function : Author
Asona Lui
  • Function : Author
Maria Elena Martinez
  • Function : Author
Brent Rose
  • Function : Author
Brandon Mahal
  • Function : Author
Kenneth Muir
  • Function : Author
Artitaya Lophatananon
  • Function : Author
Catherine Tangen
  • Function : Author
Phyllis Goodman
  • Function : Author
Ian Thompson
  • Function : Author
William Blot
  • Function : Author
Wei Zheng
Adam Kibel
  • Function : Author
Bettina Drake
  • Function : Author
Géraldine Cancel-Tassin
  • Function : Author
Florence Menegaux
  • Function : Author
Thérèse Truong
Jong Park
  • Function : Author
Hui-Yi Lin
  • Function : Author
Jack Taylor
  • Function : Author
Jeannette Bensen
  • Function : Author
James Mohler
  • Function : Author
Elizabeth Fontham
  • Function : Author
Robin Leach
  • Function : Author
Esther John
  • Function : Author
Jay Fowke
  • Function : Author
William Bush
  • Function : Author
Melinda Aldrich
  • Function : Author
Dana Crawford
  • Function : Author
Jennifer Cullen
  • Function : Author
Gyorgy Petrovics
  • Function : Author
Marie-Élise Parent
  • Function : Author
Jennifer Hu
  • Function : Author
Maureen Sanderson
  • Function : Author
Ian Mills
  • Function : Author
Ole Andreassen
  • Function : Author
Anders Dale
  • Function : Author

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.

Domains

Cancer

Dates and versions

hal-03265312 , version 1 (19-06-2021)

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Cite

Roshan Karunamuni, Minh-Phuong Huynh-Le, Chun Fan, Wesley Thompson, Asona Lui, et al.. Performance of African-ancestry-specific polygenic hazard score varies according to local ancestry in 8q24. Prostate Cancer and Prostatic Diseases, 2021, ⟨10.1038/s41391-021-00403-7⟩. ⟨hal-03265312⟩
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