Performance of different polygenic risk scores for breast cancer risk prediction: in-depth evaluations across large UK and Australian cohorts

Abstract

Polygenic risk scores (PGS) have the potential to support enhanced, risk-based screening for breast cancer. Previous studies for many diseases found that genome-wide PGS (GW-PGS) outperform PGS derived by applying hard GWAS significance thresholds. To support future breast cancer risk predictions, we compared the predictive performance of two existing PGS (including PGS313, a leading hard-thresholding PGS) and five newly developed GW-PGS (applying different methods to recent GWAS). We evaluated the performance of PGS Z-scores and of predicted 5-year absolute breast cancer risks based on age alone or age and PGS, across three large cohorts from the UK (UK Biobank) and Australia (QSkin, Melbou..