Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
Authors
Wang, AShen, J
Rodriguez, AA
Saunders, EJ
Chen, F
Janivara, R
Darst, BF
Sheng, X
Xu, Y
Chou, AJ
Benlloch, S
Dadaev, T
Brook, MN
Plym, A
Sahimi, A
Hoffman, TJ
Takahashi, A
Matsuda, K
Momozawa, Y
Fujita, M
Laisk, T
Figuerêdo, J
Muir, K
Ito, S
Liu, X
Uchio, Y
Kubo, M
Kamatani, Y
Lophatananon, A
Wan, P
Andrews, C
Lori, A
Choudhury, PP
Schleutker, J
Tammela, TLJ
Sipeky, C
Auvinen, A
Giles, GG
Southey, MC
MacInnis, RJ
Cybulski, C
Wokolorczyk, D
Lubinski, J
Rentsch, CT
Cho, K
McMahon, BH
Neal, DE
Donovan, JL
Hamdy, FC
Martin, RM
Nordestgaard, BG
Nielsen, SF
Weischer, M
Bojesen, SE
Røder, A
Stroomberg, HV
Batra, J
Chambers, S
Horvath, L
Clements, JA
Tilly, W
Risbridger, GP
Gronberg, H
Aly, M
Szulkin, R
Eklund, M
Nordstrom, T
Pashayan, N
Dunning, AM
Ghoussaini, M
Travis, RC
Key, TJ
Riboli, E
Park, JY
Sellers, TA
Lin, HY
Albanes, D
Weinstein, S
Cook, MB
Mucci, LA
Giovannucci, E
Lindstrom, S
Kraft, P
Hunter, DJ
Penney, KL
Turman, C
Tangen, CM
Goodman, PJ
Thompson, IM., Jr
Hamilton, RJ
Fleshner, NE
Finelli, A
Parent, M
Stanford, JL
Ostrander, EA
Koutros, S
Beane Freeman, LE
Stampfer, M
Wolk, A
Håkansson, N
Andriole, GL
Hoover, RN
Machiela, MJ
Sørensen, KD
Borre, M
Blot, WJ
Zheng, W
Yeboah, ED
Mensah, JE
Lu, YJ
Zhang, HW
Feng, N
Mao, X
Wu, Y
Zhao, SC
Sun, Z
Thibodeau, SN
McDonnell, SK
Schaid, DJ
West, Catherine M L
Barnett, G
Maier, C
Schnoeller, T
Luedeke, M
Kibel, AS
Drake, BF
Cussenot, O
Cancel-Tassin, G
Menegaux, F
Truong, T
Koudou, YA
John, EM
Grindedal, EM
Maehle, L
Khaw, KT
Ingles, SA
Stern, MC
Vega, A
Gómez-Caamaño, A
Fachal, L
Rosenstein, BS
Kerns, SL
Ostrer, H
Teixeira, MR
Paulo, P
Brandão, A
Watya, S
Lubwama, A
Bensen, JT
Butler, EN
Mohler, JL
Taylor, JA
Kogevinas, M
Dierssen-Sotos, T
Castaño-Vinyals, G
Cannon-Albright, L
Teerlink, CC
Huff, CD
Pilie, P
Yu, Y
Bohlender, RJ
Gu, J
Strom, SS
Multigner, L
Blanchet, P
Brureau, L
Kaneva, R
Slavov, C
Mitev, V
Leach, RJ
Brenner, H
Chen, X
Holleczek, B
Schöttker, B
Klein, EA
Hsing, AW
Kittles, RA
Murphy, AB
Logothetis, CJ
Kim, J
Neuhausen, SL
Steele, L
Ding, YC
Isaacs, WB
Nemesure, B
Hennis, AJM
Carpten, J
Pandha, H
Michael, A
De Ruyck, K
De Meerleer, G
Ost, P
Xu, J
Razack, A
Lim, J
Teo, SH
Newcomb, LF
Lin, DW
Fowke, JH
Neslund-Dudas, CM
Rybicki, BA
Gamulin, M
Lessel, D
Kulis, T
Usmani, N
Abraham, A
Singhal, S
Parliament, M
Claessens, F
Joniau, S
Van den Broeck, T
Gago-Dominguez, M
Castelao, JE
Martinez, ME
Larkin, S
Townsend, PA
Aukim-Hastie, C
Bush, WS
Aldrich, MC
Crawford, DC
Srivastava, S
Cullen, J
Petrovics, G
Casey, G
Wang, Y
Tettey, Y
Lachance, J
Tang, W
Biritwum, RB
Adjei, AA
Tay, E
Truelove, A
Niwa, S
Yamoah, K
Govindasami, K
Chokkalingam, AP
Keaton, JM
Hellwege, JN
Clark, PE
Jalloh, M
Gueye, SM
Niang, L
Ogunbiyi, O
Shittu, O
Amodu, O
Adebiyi, AO
Aisuodionoe-Shadrach, OI
Ajibola, HO
Jamda, MA
Oluwole, OP
Nwegbu, M
Adusei, B
Mante, S
Darkwa-Abrahams, A
Diop, H
Gundell, SM
Roobol, MJ
Jenster, G
van Schaik, RHN
Hu, JJ
Sanderson, M
Kachuri, L
Varma, R
McKean-Cowdin, R
Torres, M
Preuss, MH
Loos, RJF
Zawistowski, M
Zöllner, S
Lu, Z
Van Den Eeden, SK
Easton, DF
Ambs, S
Edwards, TL
Mägi, R
Rebbeck, TR
Fritsche, L
Chanock, SJ
Berndt, SI
Wiklund, F
Nakagawa, H
Witte, JS
Gaziano, JM
Justice, AC
Mancuso, N
Terao, C
Eeles, RA
Kote-Jarai, Z
Madduri, RK
Conti, DV
Haiman, CA
Affiliation
Division of Cancer Sciences, University of Manchester, Manchester Academic Health Science Centre, Radiotherapy Related Research, The Christie Hospital NHS Foundation Trust, Manchester, UKIssue Date
2023
Metadata
Show full item recordAbstract
The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.Citation
Wang A, Shen J, Rodriguez AA, Saunders EJ, Chen F, Janivara R, et al. Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants. Nature genetics. 2023 Nov 9. PubMed PMID: 37945903. Epub 2023/11/10. eng.Journal
Nature GeneticsDOI
10.1038/s41588-023-01534-4PubMed ID
37945903Additional Links
https://dx.doi.org/10.1038/s41588-023-01534-4Type
ArticleLanguage
enae974a485f413a2113503eed53cd6c53
10.1038/s41588-023-01534-4