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Evaluating approaches for constructing polygenic risk scores for prostate cancer in men of African and European ancestry

Darst, Burcu F; Shen, Jiayi; Madduri, Ravi K; Rodriguez, Alexis A; Xiao, Yukai; Sheng, Xin; Saunders, Edward J; Dadaev, Tokhir; Brook, Mark N; Hoffmann, Thomas J; Muir, Kenneth; Wan, Peggy; Le Marchand, Loic; Wilkens, Lynne; Wang, Ying; Schleutker, Johanna; MacInnis, Robert J; Cybulski, Cezary; Neal, David E; Nordestgaard, Børge G.; Nielsen, Sune F; Batra, Jyotsna; Clements, Judith A; Cancer BioResource, Australian Prostate; Grönberg, Henrik; Pashayan, Nora; Travis, Ruth C; Park, Jong Y; Albanes, Demetrius; Weinstein, Stephanie; Mucci, Lorelei A; Hunter, David J; Penney, Kathryn L; Tangen, Catherine M; Hamilton, Robert J; Parent, Marie-Élise ORCID logoORCID: https://orcid.org/0000-0002-4196-3773; Stanford, Janet L; Koutros, Stella; Wolk, Alicja; Sørensen, Karina D; Blot, William J; Yeboah, Edward D; Mensah, James E; Lu, Yong-Jie; Schaid, Daniel J; Thibodeau, Stephen N; West, Catharine M; Maier, Christiane; Kibel, Adam S; Cancel-Tassin, Géraldine; Menegaux, Florence; John, Esther M; Grindedal, Esther M; Khaw, Kay-Tee; Ingles, Sue A; Vega, Ana; Rosenstein, Barry S; Teixeira, Manuel R; Kogevinas, Manolis; Cannon-Albright, Lisa; Huff, Chad; Multigner, Luc; Kaneva, Radka; Leach, Robin J; Brenner, Hermann; Hsing, Ann W; Kittles, Rick A; Murphy, Adam B; Logothetis, Christopher J; Neuhausen, Susan L; Isaacs, William B; Nemesure, Barbara; Hennis, Anselm J; Carpten, John; Pandha, Hardev; De Ruyck, Kim; Xu, Jianfeng; Razack, Azad; Teo, Soo-Hwang; Newcomb, Lisa F; Fowke, Jay H; Neslund-Dudas, Christine; Rybicki, Benjamin A; Gamulin, Marija; Usmani, Nawaid; Claessens, Frank; Gago-Dominguez, Manuela; Castelao, Jose Esteban; Townsend, Paul A; Crawford, Dana C; Petrovics, Gyorgy; Casey, Graham; Roobol, Monique J; Hu, Jennifer F; Berndt, Sonja I; Van Den Eeden, Stephen K; Easton, Douglas F; Chanock, Stephen J; Cook, Michael B; Wiklund, Fredrik; Witte, John S; Eeles, Rosalind A; Kote-Jarai, Zsofia; Watya, Stephen; Gaziano, John M; Justice, Amy C; Conti, David V et Haiman, Christopher A (2023). Evaluating approaches for constructing polygenic risk scores for prostate cancer in men of African and European ancestry American journal of human genetics , vol. 110 , nº 7. pp. 1200-1206.

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Résumé


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 (PRS(269)). 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 PRS(269). 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 PRS(269) 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 PRS(269) developed from multi-ancestry GWASs and fine-mapping.

Type de document: Article
Mots-clés libres: African ancestry; genetics; genome-wide polygenic risk score; health disparities; polygenic risk score; prostate cancer; risk modeling.
Centre: Centre INRS-Institut Armand Frappier
Date de dépôt: 30 déc. 2023 22:08
Dernière modification: 30 déc. 2023 22:08
URI: https://espace.inrs.ca/id/eprint/13632

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