TY - JOUR
T1 - Evaluation of European-based polygenic risk score for breast cancer in Ashkenazi Jewish women in Israel
AU - Levi, Hagai
AU - Michailidou, Kyriaki
AU - Ahearn, Thomas
AU - Andrulis, Irene L
AU - Anton-Culver, Hoda
AU - Antoniou, Antonis C
AU - Arndt, Volker
AU - Augustinsson, Annelie
AU - Bermisheva, Marina
AU - Bodelon, Clara
AU - Bogdanova, Natalia V
AU - Bojesen, Stig E
AU - Brenner, Hermann
AU - Byers, Helen
AU - Dossus, Laure
AU - Eccles, Diana M
AU - Eliassen, A Heather
AU - Eriksson, Mikael
AU - Evans, Gareth
AU - Fasching, Peter
AU - Hall, Per
AU - Jernström, Helena
AU - Elkon, Ran
AU - BCAC Consortium
AU - NBCS Collaborators
AU - ABCTB Investigators
N1 - © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.
PY - 2023
Y1 - 2023
N2 - BACKGROUND: Polygenic risk score (PRS), calculated based on genome-wide association studies (GWASs), can improve breast cancer (BC) risk assessment. To date, most BC GWASs have been performed in individuals of European (EUR) ancestry, and the generalisation of EUR-based PRS to other populations is a major challenge. In this study, we examined the performance of EUR-based BC PRS models in Ashkenazi Jewish (AJ) women.METHODS: We generated PRSs based on data on EUR women from the Breast Cancer Association Consortium (BCAC). We tested the performance of the PRSs in a cohort of 2161 AJ women from Israel (1437 cases and 724 controls) from BCAC (BCAC cohort from Israel (BCAC-IL)). In addition, we tested the performance of these EUR-based BC PRSs, as well as the established 313-SNP EUR BC PRS, in an independent cohort of 181 AJ women from Hadassah Medical Center (HMC) in Israel.RESULTS: In the BCAC-IL cohort, the highest OR per 1 SD was 1.56 (±0.09). The OR for AJ women at the top 10% of the PRS distribution compared with the middle quintile was 2.10 (±0.24). In the HMC cohort, the OR per 1 SD of the EUR-based PRS that performed best in the BCAC-IL cohort was 1.58±0.27. The OR per 1 SD of the commonly used 313-SNP BC PRS was 1.64 (±0.28).CONCLUSIONS: Extant EUR GWAS data can be used for generating PRSs that identify AJ women with markedly elevated risk of BC and therefore hold promise for improving BC risk assessment in AJ women.
AB - BACKGROUND: Polygenic risk score (PRS), calculated based on genome-wide association studies (GWASs), can improve breast cancer (BC) risk assessment. To date, most BC GWASs have been performed in individuals of European (EUR) ancestry, and the generalisation of EUR-based PRS to other populations is a major challenge. In this study, we examined the performance of EUR-based BC PRS models in Ashkenazi Jewish (AJ) women.METHODS: We generated PRSs based on data on EUR women from the Breast Cancer Association Consortium (BCAC). We tested the performance of the PRSs in a cohort of 2161 AJ women from Israel (1437 cases and 724 controls) from BCAC (BCAC cohort from Israel (BCAC-IL)). In addition, we tested the performance of these EUR-based BC PRSs, as well as the established 313-SNP EUR BC PRS, in an independent cohort of 181 AJ women from Hadassah Medical Center (HMC) in Israel.RESULTS: In the BCAC-IL cohort, the highest OR per 1 SD was 1.56 (±0.09). The OR for AJ women at the top 10% of the PRS distribution compared with the middle quintile was 2.10 (±0.24). In the HMC cohort, the OR per 1 SD of the EUR-based PRS that performed best in the BCAC-IL cohort was 1.58±0.27. The OR per 1 SD of the commonly used 313-SNP BC PRS was 1.64 (±0.28).CONCLUSIONS: Extant EUR GWAS data can be used for generating PRSs that identify AJ women with markedly elevated risk of BC and therefore hold promise for improving BC risk assessment in AJ women.
U2 - 10.1136/jmg-2023-109185
DO - 10.1136/jmg-2023-109185
M3 - Article
C2 - 37451831
SN - 0022-2593
VL - 60
SP - 1186
EP - 1197
JO - Journal of Medical Genetics
JF - Journal of Medical Genetics
IS - 12
ER -
