TY - UNPB
T1 - Differences in polygenic score distributions in European ancestry populations
T2 - implications for breast cancer risk prediction
AU - NBCS Collaborators
AU - Yiangou, Kristia
AU - Mavaddat, Nasim
AU - Dennis, Joe
AU - Zanti, Maria
AU - Wang, Qin
AU - Bolla, Manjeet K
AU - Abubakar, Mustapha
AU - Ahearn, Thomas U
AU - Andrulis, Irene L
AU - Anton-Culver, Hoda
AU - Antonenkova, Natalia N
AU - Arndt, Volker
AU - Aronson, Kristan J
AU - Augustinsson, Annelie
AU - Baten, Adinda
AU - Behrens, Sabine
AU - Bermisheva, Marina
AU - de Gonzalez, Amy Berrington
AU - Białkowska, Katarzyna
AU - Boddicker, Nicholas
AU - Bodelon, Clara
AU - Bogdanova, Natalia V
AU - Bojesen, Stig E
AU - Brantley, Kristen D
AU - Brauch, Hiltrud
AU - Brenner, Hermann
AU - Camp, Nicola J
AU - Canzian, Federico
AU - Castelao, Jose E
AU - Cessna, Melissa H
AU - Chang-Claude, Jenny
AU - Chenevix-Trench, Georgia
AU - Chung, Wendy K
AU - Colonna, Sarah V
AU - Couch, Fergus J
AU - Cox, Angela
AU - Cross, Simon S
AU - Czene, Kamila
AU - Daly, Mary B
AU - Devilee, Peter
AU - Dörk, Thilo
AU - Dunning, Alison M
AU - Evans, D Gareth
AU - Howell, Sacha
AU - Howell, Anthony
AU - Patel, Alpa V
AU - Peng, Cheng
AU - Roberts, Eleanor
AU - Scott, Christopher G
AU - Zheng, Wei
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
T3 - medRxiv
BT - Differences in polygenic score distributions in European ancestry populations
PB - Cold Spring Harbor Laboratory Press
ER -
