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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants.

Authors :
Wang, A
Shen, 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
Biobank Japan Project
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, H-Y
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
Hamilton, RJ
Fleshner, NE
Finelli, A
Parent, M-É
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, Y-J
Zhang, H-W
Feng, N
Mao, X
Wu, Y
Zhao, S-C
Sun, Z
Thibodeau, SN
McDonnell, SK
Schaid, DJ
West, CML
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, K-T
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, S-H
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
Wang, A
Shen, 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
Biobank Japan Project
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, H-Y
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
Hamilton, RJ
Fleshner, NE
Finelli, A
Parent, M-É
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, Y-J
Zhang, H-W
Feng, N
Mao, X
Wu, Y
Zhao, S-C
Sun, Z
Thibodeau, SN
McDonnell, SK
Schaid, DJ
West, CML
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, K-T
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, S-H
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
Publication Year :
2023

Abstract

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.

Details

Database :
OAIster
Publication Type :
Electronic Resource
Accession number :
edsoai.on1414443157
Document Type :
Electronic Resource