TY - UNPB

T1 - Differences in polygenic score distributions in European ancestry populations: implications for breast cancer risk prediction

AU - NBCS Collaborators

AU - ABCTB Investigators

AU - KConFab Investigators

AU - Хуснутдинова, Эльза Камилевна

AU - Бермишева, Марина Алексеевна

PY - 2024/2/13

Y1 - 2024/2/13

N2 - The 313-variant polygenic risk score (PRS 313) provides a promising tool for breast cancer risk prediction. However, evaluation of the PRS 313 across different European populations which could influence risk estimation has not been performed. Here, we explored the distribution of PRS 313 across European populations using genotype data from 94,072 females without breast cancer, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 225,105 female participants from the UK Biobank. The mean PRS 313 differed markedly across European countries, being highest in south-eastern Europe and lowest in north-western Europe. Using the overall European PRS 313 distribution to categorise individuals leads to overestimation and underestimation of risk in some individuals from south-eastern and north-western countries, respectively. Adjustment for principal components explained most of the observed heterogeneity in mean PRS. Country-specific PRS distributions may be used to calibrate risk categories in individuals from different countries.

AB - The 313-variant polygenic risk score (PRS 313) provides a promising tool for breast cancer risk prediction. However, evaluation of the PRS 313 across different European populations which could influence risk estimation has not been performed. Here, we explored the distribution of PRS 313 across European populations using genotype data from 94,072 females without breast cancer, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 225,105 female participants from the UK Biobank. The mean PRS 313 differed markedly across European countries, being highest in south-eastern Europe and lowest in north-western Europe. Using the overall European PRS 313 distribution to categorise individuals leads to overestimation and underestimation of risk in some individuals from south-eastern and north-western countries, respectively. Adjustment for principal components explained most of the observed heterogeneity in mean PRS. Country-specific PRS distributions may be used to calibrate risk categories in individuals from different countries.

U2 - 10.1101/2024.02.12.24302043

DO - 10.1101/2024.02.12.24302043

M3 - Preprint

C2 - 38410445

BT - Differences in polygenic score distributions in European ancestry populations: implications for breast cancer risk prediction

ER -