| Title: | Assessing the risk stratification of breast cancer polygenic risk scores in a Brazilian cohort |
| Journal: | Journal of Molecular Diagnostics |
| Published: | 6 Jul 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38972593/ |
| DOI: | https://doi.org/10.1016/j.jmoldx.2024.06.002 |
Publication 11699
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Abstract
Polygenic risk scores (PRSs) for breast cancer have a clear clinical utility in risk prediction. PRS transferability across populations and ancestry groups is hampered by population-specific factors, ultimately leading to differences in variant effects, such as linkage disequilibrium and differences in variant frequency (allele frequency differences). Thus, locally sourced population-based phenotypic and genomic data sets are essential to assess the validity of PRSs derived from signals detected across populations. Here, we assess the transferability of a breast cancer PRS composed of 313 risk variants (313-PRS) in a Brazilian trihybrid admixed ancestries (European, African, and Native American) whole-genome sequenced cohort, the Rare Genomes Project. We computed 313-PRS in the Rare Genomes Project (n = 853) using the UK Biobank (UKBB; n = 264,307) as reference. We show that although the Brazilian cohorts have a high European ancestry (EA) component, with allele frequency differences and to a lesser extent linkage disequilibrium patterns similar to those found in EA populations, the 313-PRS distribution is inflated when compared with that of the UKBB, leading to potential overestimation of PRS-based risk if EA is taken as a standard. Interestingly, we find that case controls lead to equivalent predictive power when compared with UKBB-EA samples with area under the receiver operating characteristic curve values of 0.66 to 0.62 compared with 0.63 for UKBB.</p>
18 Authors
- Rodrigo Araujo Sequeira Barreiro
- Tatiana Ferreira de Almeida
- Catarina Dos Santos Gomes
- Frederico Monfardini
- Allysson Allan de Farias
- Gabriela Chiuffa Tunes
- Gabriel Mesquita de Souza
- Etienne Duim
- Jaqueline de Sá Correia
- Antonio Victor Campos Coelho
- Marcel Pinheiro Caraciolo
- Yeda Aparecida Oliveira Duarte
- Mayana Zatz
- Edson Amaro
- João Bosco Oliveira
- Bárbara Domingues Bitarello
- Helena Brentani
- Michel Satya Naslavsky
1 Application
| Application ID | Title |
|---|---|
| 74348 | Assessing and evaluating polygenic scores of complex phenotypic traits in admixed populations |
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