TY - JOUR
T1 - Evaluating approaches for constructing polygenic risk scores for prostate cancer in men of African and European ancestry
AU - NC-LA PCaP Investigators
AU - Canary PASS Investigators
AU - Darst, Burcu F.
AU - Shen, Jiayi
AU - Madduri, Ravi K.
AU - Rodriguez, Alexis A.
AU - Xiao, Yukai
AU - Sheng, Xin
AU - Saunders, Edward J.
AU - Dadaev, Tokhir
AU - Brook, Mark N.
AU - Hoffmann, Thomas J.
AU - Muir, Kenneth
AU - Wan, Peggy
AU - Le Marchand, Loic
AU - Wilkens, Lynne
AU - Wang, Ying
AU - Schleutker, Johanna
AU - MacInnis, Robert J.
AU - Cybulski, Cezary
AU - Neal, David E.
AU - Nordestgaard, Børge G.
AU - Nielsen, Sune F.
AU - Batra, Jyotsna
AU - Clements, Judith A.
AU - Cancer BioResource, Australian Prostate
AU - Grönberg, Henrik
AU - Pashayan, Nora
AU - Travis, Ruth C.
AU - Park, Jong Y.
AU - Albanes, Demetrius
AU - Weinstein, Stephanie
AU - Mucci, Lorelei A.
AU - Hunter, David J.
AU - Penney, Kathryn L.
AU - Tangen, Catherine M.
AU - Hamilton, Robert J.
AU - Parent, Marie Élise
AU - Stanford, Janet L.
AU - Koutros, Stella
AU - Wolk, Alicja
AU - Sørensen, Karina D.
AU - Blot, William J.
AU - Yeboah, Edward D.
AU - Mensah, James E.
AU - Lu, Yong Jie
AU - Schaid, Daniel J.
AU - Thibodeau, Stephen N.
AU - West, Catharine M.
AU - Maier, Christiane
AU - Kibel, Adam S.
AU - Cancel-Tassin, Géraldine
N1 - Publisher Copyright:
© 2023 American Society of Human Genetics
PY - 2023/7/6
Y1 - 2023/7/6
N2 - Genome-wide polygenic risk scores (GW-PRSs) have been reported to have better predictive ability than PRSs based on genome-wide significance thresholds across numerous traits. We compared the predictive ability of several GW-PRS approaches to a recently developed PRS of 269 established prostate cancer-risk variants from multi-ancestry GWASs and fine-mapping studies (PRS269). GW-PRS models were trained with a large and diverse prostate cancer GWAS of 107,247 cases and 127,006 controls that we previously used to develop the multi-ancestry PRS269. Resulting models were independently tested in 1,586 cases and 1,047 controls of African ancestry from the California Uganda Study and 8,046 cases and 191,825 controls of European ancestry from the UK Biobank and further validated in 13,643 cases and 210,214 controls of European ancestry and 6,353 cases and 53,362 controls of African ancestry from the Million Veteran Program. In the testing data, the best performing GW-PRS approach had AUCs of 0.656 (95% CI = 0.635–0.677) in African and 0.844 (95% CI = 0.840–0.848) in European ancestry men and corresponding prostate cancer ORs of 1.83 (95% CI = 1.67–2.00) and 2.19 (95% CI = 2.14–2.25), respectively, for each SD unit increase in the GW-PRS. Compared to the GW-PRS, in African and European ancestry men, the PRS269 had larger or similar AUCs (AUC = 0.679, 95% CI = 0.659–0.700 and AUC = 0.845, 95% CI = 0.841–0.849, respectively) and comparable prostate cancer ORs (OR = 2.05, 95% CI = 1.87–2.26 and OR = 2.21, 95% CI = 2.16–2.26, respectively). Findings were similar in the validation studies. This investigation suggests that current GW-PRS approaches may not improve the ability to predict prostate cancer risk compared to the PRS269 developed from multi-ancestry GWASs and fine-mapping.
AB - Genome-wide polygenic risk scores (GW-PRSs) have been reported to have better predictive ability than PRSs based on genome-wide significance thresholds across numerous traits. We compared the predictive ability of several GW-PRS approaches to a recently developed PRS of 269 established prostate cancer-risk variants from multi-ancestry GWASs and fine-mapping studies (PRS269). GW-PRS models were trained with a large and diverse prostate cancer GWAS of 107,247 cases and 127,006 controls that we previously used to develop the multi-ancestry PRS269. Resulting models were independently tested in 1,586 cases and 1,047 controls of African ancestry from the California Uganda Study and 8,046 cases and 191,825 controls of European ancestry from the UK Biobank and further validated in 13,643 cases and 210,214 controls of European ancestry and 6,353 cases and 53,362 controls of African ancestry from the Million Veteran Program. In the testing data, the best performing GW-PRS approach had AUCs of 0.656 (95% CI = 0.635–0.677) in African and 0.844 (95% CI = 0.840–0.848) in European ancestry men and corresponding prostate cancer ORs of 1.83 (95% CI = 1.67–2.00) and 2.19 (95% CI = 2.14–2.25), respectively, for each SD unit increase in the GW-PRS. Compared to the GW-PRS, in African and European ancestry men, the PRS269 had larger or similar AUCs (AUC = 0.679, 95% CI = 0.659–0.700 and AUC = 0.845, 95% CI = 0.841–0.849, respectively) and comparable prostate cancer ORs (OR = 2.05, 95% CI = 1.87–2.26 and OR = 2.21, 95% CI = 2.16–2.26, respectively). Findings were similar in the validation studies. This investigation suggests that current GW-PRS approaches may not improve the ability to predict prostate cancer risk compared to the PRS269 developed from multi-ancestry GWASs and fine-mapping.
KW - African ancestry
KW - genetics
KW - genome-wide polygenic risk score
KW - health disparities
KW - polygenic risk score
KW - prostate cancer
KW - risk modeling
UR - https://www.scopus.com/pages/publications/85165069171
U2 - 10.1016/j.ajhg.2023.05.010
DO - 10.1016/j.ajhg.2023.05.010
M3 - Article
AN - SCOPUS:85165069171
SN - 0002-9297
VL - 110
SP - 1200
EP - 1206
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
IS - 7
ER -
SDG 3 Good Health and Well-being