乳腺癌 (BC) 的多基因风险评分 (PRS) 在风险预测方面具有明确的临床效用。 PRS 在人群和血统群体之间的可转移性受到人群特定因素的阻碍，最终导致变异效应的差异，例如连锁不平衡 (LD) 和变异频率的差异 (AF-diff)。因此，本地来源的基于人群的表型和基因组数据集对于评估从跨人群检测到的信号衍生的 PRS 的有效性至关重要。在这里，我们评估了巴西三杂交混合血统（欧洲、非洲和美洲原住民）全基因组测序队列 GRAR 中由 313 个风险变异 (313-PRS) 组成的 BC PRS 的可转移性。我们使用英国生物库（UKBB，n=264,307）作为参考计算 GRAR（n=853）中的 313-PRS。我们表明，尽管巴西人群具有较高的欧洲 (EA) 成分，并且具有 AF-diff 和较小程度的 LD 模式，与 EA 人群中发现的相似，但与 UKBB 相比，313-PRS 分布有所夸大，如果将 EA 作为标准，则可能会高估基于 PRS 的风险。有趣的是，我们发现，与 UKBB-EA 样本相比，病例对照具有相同的预测能力，AUROC 值为 0.66-0.62，而 UKBB 为 0.63。版权所有 © 2024。由 Elsevier Inc. 出版。

Polygenic risk scores (PRS) for breast cancer (BC) 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 (LD) and differences in variant frequency (AF-diff). Thus, locally-sourced population-based phenotypic and genomic datasets are essential to assess the validity of PRS derived from signals detected across populations. Here, we assess the transferability of a BC PRS composed of 313 risk variants (313-PRS) in a Brazilian tri-hybrid admixed ancestries (European, African and Native American) whole-genome sequenced cohort, GRAR. We computed 313-PRS in GRAR (n=853) using the UK Biobank (UKBB, n=264,307) as reference. We show that although the Brazilian cohorts have a high European (EA) component, with AF-diff and to a lesser extent LD patterns similar to those found in EA populations, the 313-PRS distribution is inflated when compared to 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 to UKBB-EA samples with AUROC values of 0.66-0.62 compared to 0.63 for UKBB.Copyright © 2024. Published by Elsevier Inc.