| 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. This study assesses 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. 313-PRS was computed in the Rare Genomes Project (n = 853) using the UK Biobank (UKBB; n = 264,307) as reference. 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 was found to be inflated when compared with that of the UKBB, leading to potential overestimation of PRS-based risk if EA is taken as a standard. However, 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>
15 Keywords
- Brazil
- Breast Neoplasms
- Case-Control Studies
- Cohort Studies
- Female
- Gene Frequency
- Genetic Predisposition to Disease
- Genetic Risk Score
- Genome-Wide Association Study
- Humans
- Linkage Disequilibrium
- Multifactorial Inheritance
- Polymorphism, Single Nucleotide
- Risk Assessment
- Risk Factors
18 Authors
- Rodrigo A S Barreiro
- Tatiana F de Almeida
- Catarina Gomes
- Frederico Monfardini
- Allysson A de Farias
- Gabriela C Tunes
- Gabriel M de Souza
- Etienne Duim
- Jaqueline de Sá Correia
- Antonio V Campos Coelho
- Marcel P Caraciolo
- Yeda A Oliveira Duarte
- Mayana Zatz
- Edson Amaro
- João B Oliveira
- Bárbara D Bitarello
- Helena Brentani
- Michel S Naslavsky
1 Application
| Application ID | Title |
|---|---|
| 74348 | Assessing and evaluating polygenic scores of complex phenotypic traits in admixed populations |
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