Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants. / Wang, Anqi; Shen, Jiayi; Rodriguez, Alex A; Saunders, Edward J; Chen, Fei; Janivara, Rohini; Darst, Burcu F; Sheng, Xin; Xu, Yili; Chou, Alisha J; Benlloch, Sara; Dadaev, Tokhir; Brook, Mark N; Plym, Anna; Sahimi, Ali; Hoffman, Thomas J; Takahashi, Atushi; Matsuda, Koichi; Momozawa, Yukihide; Fujita, Masashi; Laisk, Triin; Figuerêdo, Jéssica; Muir, Kenneth; Ito, Shuji; Liu, Xiaoxi; Uchio, Yuji; Kubo, Michiaki; Kamatani, Yoichiro; Lophatananon, Artitaya; Wan, Peggy; Andrews, Caroline; Lori, Adriana; Choudhury, Parichoy P; Schleutker, Johanna; Tammela, Teuvo L J; Sipeky, Csilla; Auvinen, Anssi; Giles, Graham G; Southey, Melissa C; MacInnis, Robert J; Cybulski, Cezary; Wokolorczyk, Dominika; Lubinski, Jan; Rentsch, Christopher T; Cho, Kelly; Mcmahon, Benjamin H; Neal, David E; Donovan, Jenny L; Hamdy, Freddie C; Martin, Richard M; Nordestgaard, Borge G; Nielsen, Sune F; Weischer, Maren; Bojesen, Stig E; Røder, Andreas; Stroomberg, Hein V; Batra, Jyotsna; Chambers, Suzanne; Horvath, Lisa; Clements, Judith A; Tilly, Wayne; Risbridger, Gail P; Gronberg, Henrik; Aly, Markus; Szulkin, Robert; Eklund, Martin; Nordstrom, Tobias; Pashayan, Nora; Dunning, Alison M; Ghoussaini, Maya; Travis, Ruth C; Key, Tim J; Riboli, Elio; Park, Jong Y; Sellers, Thomas A; Lin, Hui-Yi; Albanes, Demetrius; Weinstein, Stephanie; Cook, Michael B; Mucci, Lorelei A; Giovannucci, Edward; Lindstrom, Sara; Kraft, Peter; Hunter, David J; Penney, Kathryn L; Turman, Constance; Tangen, Catherine M; Goodman, Phyllis J; Thompson, Ian M; Hamilton, Robert J; Fleshner, Neil E; Finelli, Antonio; Parent, Marie-Élise; Stanford, Janet L; Ostrander, Elaine A; Koutros, Stella; Beane Freeman, Laura E; Stampfer, Meir; Wolk, Alicja; Håkansson, Niclas; Andriole, Gerald L; Hoover, Robert N; Machiela, Mitchell J; Sørensen, Karina Dalsgaard; Borre, Michael; Blot, William J; Zheng, Wei; Yeboah, Edward D; Mensah, James E; Lu, Yong-Jie; Zhang, Hong-Wei; Feng, Ninghan; Mao, Xueying; Wu, Yudong; Zhao, Shan-Chao; Sun, Zan; Thibodeau, Stephen N; McDonnell, Shannon K; Schaid, Daniel J; West, Catharine M L; Barnett, Gill; Maier, Christiane; Schnoeller, Thomas; Luedeke, Manuel; Kibel, Adam S; Drake, Bettina F; Cussenot, Olivier; Cancel-Tassin, Geraldine; Menegaux, Florence; Truong, Thérèse; Koudou, Yves Akoli; John, Esther M; Grindedal, Eli Marie; Maehle, Lovise; Khaw, Kay-Tee; Ingles, Sue A; Stern, Mariana C; Vega, Ana; Gómez-Caamaño, Antonio; Fachal, Laura; Rosenstein, Barry S; Kerns, Sarah L; Ostrer, Harry; Teixeira, Manuel R; Paulo, Paula; Brandão, Andreia; Watya, Stephen; Lubwama, Alexander; Bensen, Jeannette T; Butler, Ebonee N; Mohler, James L; Taylor, Jack A; Kogevinas, Manolis; Dierssen-Sotos, Trinidad; Castaño-Vinyals, Gemma; Cannon-Albright, Lisa; Teerlink, Craig C; Huff, Chad D; Pilie, Patrick; Yu, Yao; Bohlender, Ryan J; Gu, Jian; Strom, Sara S; Multigner, Luc; Blanchet, Pascal; Brureau, Laurent; Kaneva, Radka; Slavov, Chavdar; Mitev, Vanio; Leach, Robin J; Brenner, Hermann; Chen, Xuechen; Holleczek, Bernd; Schöttker, Ben; Klein, Eric A; Hsing, Ann W; Kittles, Rick A; Murphy, Adam B; Logothetis, Christopher J; Kim, Jeri; Neuhausen, Susan L; Steele, Linda; Ding, Yuan Chun; Isaacs, William B; Nemesure, Barbara; Hennis, Anselm J M; Carpten, John; Pandha, Hardev; Michael, Agnieszka; De Ruyck, Kim; De Meerleer, Gert; Ost, Piet; Xu, Jianfeng; Razack, Azad; Lim, Jasmine; Teo, Soo-Hwang; Newcomb, Lisa F; Lin, Daniel W; Fowke, Jay H; Neslund-Dudas, Christine M; Rybicki, Benjamin A; Gamulin, Marija; Lessel, Davor; Kulis, Tomislav; Usmani, Nawaid; Abraham, Aswin; Singhal, Sandeep; Parliament, Matthew; Claessens, Frank; Joniau, Steven; Van den Broeck, Thomas; Gago-Dominguez, Manuela; Castelao, Jose Esteban; Martinez, Maria Elena; Larkin, Samantha; Townsend, Paul A; Aukim-Hastie, Claire; Bush, William S; Aldrich, Melinda C; Crawford, Dana C; Srivastava, Shiv; Cullen, Jennifer; Petrovics, Gyorgy; Casey, Graham; Wang, Ying; Tettey, Yao; Lachance, Joseph; Tang, Wei; Biritwum, Richard B; Adjei, Andrew A; Tay, Evelyn; Truelove, Ann; Niwa, Shelley; Yamoah, Kosj; Govindasami, Koveela; Chokkalingam, Anand P; Keaton, Jacob M; Hellwege, Jacklyn N; Clark, Peter E; Jalloh, Mohamed; Gueye, Serigne M; Niang, Lamine; Ogunbiyi, Olufemi; Shittu, Olayiwola; Amodu, Olukemi; Adebiyi, Akindele O; Aisuodionoe-Shadrach, Oseremen I; Ajibola, Hafees O; Jamda, Mustapha A; Oluwole, Olabode P; Nwegbu, Maxwell; Adusei, Ben; Mante, Sunny; Darkwa-Abrahams, Afua; Diop, Halimatou; Gundell, Susan M; Roobol, Monique J; Jenster, Guido; van Schaik, Ron H N; Hu, Jennifer J; Sanderson, Maureen; Kachuri, Linda; Varma, Rohit; McKean-Cowdin, Roberta; Torres, Mina; Preuss, Michael H; Loos, Ruth J F; Zawistowski, Matthew; Zöllner, Sebastian; Lu, Zeyun; Van Den Eeden, Stephen K; Easton, Douglas F; Ambs, Stefan; Edwards, Todd L; Mägi, Reedik; Rebbeck, Timothy R; Fritsche, Lars; Chanock, Stephen J; Berndt, Sonja I; Wiklund, Fredrik; Nakagawa, Hidewaki; Witte, John S; Gaziano, J Michael; Justice, Amy C; Mancuso, Nick; Terao, Chikashi; BioBank Japan Project; Eeles, Rosalind A; Kote-Jarai, Zsofia; Madduri, Ravi K; Conti, David V; Haiman, Christopher A.
in: NAT GENET, Jahrgang 55, Nr. 12, 12.2023, S. 2065-2074.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
AU - Wang, Anqi
AU - Shen, Jiayi
AU - Rodriguez, Alex A
AU - Saunders, Edward J
AU - Chen, Fei
AU - Janivara, Rohini
AU - Darst, Burcu F
AU - Sheng, Xin
AU - Xu, Yili
AU - Chou, Alisha J
AU - Benlloch, Sara
AU - Dadaev, Tokhir
AU - Brook, Mark N
AU - Plym, Anna
AU - Sahimi, Ali
AU - Hoffman, Thomas J
AU - Takahashi, Atushi
AU - Matsuda, Koichi
AU - Momozawa, Yukihide
AU - Fujita, Masashi
AU - Laisk, Triin
AU - Figuerêdo, Jéssica
AU - Muir, Kenneth
AU - Ito, Shuji
AU - Liu, Xiaoxi
AU - Uchio, Yuji
AU - Kubo, Michiaki
AU - Kamatani, Yoichiro
AU - Lophatananon, Artitaya
AU - Wan, Peggy
AU - Andrews, Caroline
AU - Lori, Adriana
AU - Choudhury, Parichoy P
AU - Schleutker, Johanna
AU - Tammela, Teuvo L J
AU - Sipeky, Csilla
AU - Auvinen, Anssi
AU - Giles, Graham G
AU - Southey, Melissa C
AU - MacInnis, Robert J
AU - Cybulski, Cezary
AU - Wokolorczyk, Dominika
AU - Lubinski, Jan
AU - Rentsch, Christopher T
AU - Cho, Kelly
AU - Mcmahon, Benjamin H
AU - Neal, David E
AU - Donovan, Jenny L
AU - Hamdy, Freddie C
AU - Martin, Richard M
AU - Nordestgaard, Borge G
AU - Nielsen, Sune F
AU - Weischer, Maren
AU - Bojesen, Stig E
AU - Røder, Andreas
AU - Stroomberg, Hein V
AU - Batra, Jyotsna
AU - Chambers, Suzanne
AU - Horvath, Lisa
AU - Clements, Judith A
AU - Tilly, Wayne
AU - Risbridger, Gail P
AU - Gronberg, Henrik
AU - Aly, Markus
AU - Szulkin, Robert
AU - Eklund, Martin
AU - Nordstrom, Tobias
AU - Pashayan, Nora
AU - Dunning, Alison M
AU - Ghoussaini, Maya
AU - Travis, Ruth C
AU - Key, Tim J
AU - Riboli, Elio
AU - Park, Jong Y
AU - Sellers, Thomas A
AU - Lin, Hui-Yi
AU - Albanes, Demetrius
AU - Weinstein, Stephanie
AU - Cook, Michael B
AU - Mucci, Lorelei A
AU - Giovannucci, Edward
AU - Lindstrom, Sara
AU - Kraft, Peter
AU - Hunter, David J
AU - Penney, Kathryn L
AU - Turman, Constance
AU - Tangen, Catherine M
AU - Goodman, Phyllis J
AU - Thompson, Ian M
AU - Hamilton, Robert J
AU - Fleshner, Neil E
AU - Finelli, Antonio
AU - Parent, Marie-Élise
AU - Stanford, Janet L
AU - Ostrander, Elaine A
AU - Koutros, Stella
AU - Beane Freeman, Laura E
AU - Stampfer, Meir
AU - Wolk, Alicja
AU - Håkansson, Niclas
AU - Andriole, Gerald L
AU - Hoover, Robert N
AU - Machiela, Mitchell J
AU - Sørensen, Karina Dalsgaard
AU - Borre, Michael
AU - Blot, William J
AU - Zheng, Wei
AU - Yeboah, Edward D
AU - Mensah, James E
AU - Lu, Yong-Jie
AU - Zhang, Hong-Wei
AU - Feng, Ninghan
AU - Mao, Xueying
AU - Wu, Yudong
AU - Zhao, Shan-Chao
AU - Sun, Zan
AU - Thibodeau, Stephen N
AU - McDonnell, Shannon K
AU - Schaid, Daniel J
AU - West, Catharine M L
AU - Barnett, Gill
AU - Maier, Christiane
AU - Schnoeller, Thomas
AU - Luedeke, Manuel
AU - Kibel, Adam S
AU - Drake, Bettina F
AU - Cussenot, Olivier
AU - Cancel-Tassin, Geraldine
AU - Menegaux, Florence
AU - Truong, Thérèse
AU - Koudou, Yves Akoli
AU - John, Esther M
AU - Grindedal, Eli Marie
AU - Maehle, Lovise
AU - Khaw, Kay-Tee
AU - Ingles, Sue A
AU - Stern, Mariana C
AU - Vega, Ana
AU - Gómez-Caamaño, Antonio
AU - Fachal, Laura
AU - Rosenstein, Barry S
AU - Kerns, Sarah L
AU - Ostrer, Harry
AU - Teixeira, Manuel R
AU - Paulo, Paula
AU - Brandão, Andreia
AU - Watya, Stephen
AU - Lubwama, Alexander
AU - Bensen, Jeannette T
AU - Butler, Ebonee N
AU - Mohler, James L
AU - Taylor, Jack A
AU - Kogevinas, Manolis
AU - Dierssen-Sotos, Trinidad
AU - Castaño-Vinyals, Gemma
AU - Cannon-Albright, Lisa
AU - Teerlink, Craig C
AU - Huff, Chad D
AU - Pilie, Patrick
AU - Yu, Yao
AU - Bohlender, Ryan J
AU - Gu, Jian
AU - Strom, Sara S
AU - Multigner, Luc
AU - Blanchet, Pascal
AU - Brureau, Laurent
AU - Kaneva, Radka
AU - Slavov, Chavdar
AU - Mitev, Vanio
AU - Leach, Robin J
AU - Brenner, Hermann
AU - Chen, Xuechen
AU - Holleczek, Bernd
AU - Schöttker, Ben
AU - Klein, Eric A
AU - Hsing, Ann W
AU - Kittles, Rick A
AU - Murphy, Adam B
AU - Logothetis, Christopher J
AU - Kim, Jeri
AU - Neuhausen, Susan L
AU - Steele, Linda
AU - Ding, Yuan Chun
AU - Isaacs, William B
AU - Nemesure, Barbara
AU - Hennis, Anselm J M
AU - Carpten, John
AU - Pandha, Hardev
AU - Michael, Agnieszka
AU - De Ruyck, Kim
AU - De Meerleer, Gert
AU - Ost, Piet
AU - Xu, Jianfeng
AU - Razack, Azad
AU - Lim, Jasmine
AU - Teo, Soo-Hwang
AU - Newcomb, Lisa F
AU - Lin, Daniel W
AU - Fowke, Jay H
AU - Neslund-Dudas, Christine M
AU - Rybicki, Benjamin A
AU - Gamulin, Marija
AU - Lessel, Davor
AU - Kulis, Tomislav
AU - Usmani, Nawaid
AU - Abraham, Aswin
AU - Singhal, Sandeep
AU - Parliament, Matthew
AU - Claessens, Frank
AU - Joniau, Steven
AU - Van den Broeck, Thomas
AU - Gago-Dominguez, Manuela
AU - Castelao, Jose Esteban
AU - Martinez, Maria Elena
AU - Larkin, Samantha
AU - Townsend, Paul A
AU - Aukim-Hastie, Claire
AU - Bush, William S
AU - Aldrich, Melinda C
AU - Crawford, Dana C
AU - Srivastava, Shiv
AU - Cullen, Jennifer
AU - Petrovics, Gyorgy
AU - Casey, Graham
AU - Wang, Ying
AU - Tettey, Yao
AU - Lachance, Joseph
AU - Tang, Wei
AU - Biritwum, Richard B
AU - Adjei, Andrew A
AU - Tay, Evelyn
AU - Truelove, Ann
AU - Niwa, Shelley
AU - Yamoah, Kosj
AU - Govindasami, Koveela
AU - Chokkalingam, Anand P
AU - Keaton, Jacob M
AU - Hellwege, Jacklyn N
AU - Clark, Peter E
AU - Jalloh, Mohamed
AU - Gueye, Serigne M
AU - Niang, Lamine
AU - Ogunbiyi, Olufemi
AU - Shittu, Olayiwola
AU - Amodu, Olukemi
AU - Adebiyi, Akindele O
AU - Aisuodionoe-Shadrach, Oseremen I
AU - Ajibola, Hafees O
AU - Jamda, Mustapha A
AU - Oluwole, Olabode P
AU - Nwegbu, Maxwell
AU - Adusei, Ben
AU - Mante, Sunny
AU - Darkwa-Abrahams, Afua
AU - Diop, Halimatou
AU - Gundell, Susan M
AU - Roobol, Monique J
AU - Jenster, Guido
AU - van Schaik, Ron H N
AU - Hu, Jennifer J
AU - Sanderson, Maureen
AU - Kachuri, Linda
AU - Varma, Rohit
AU - McKean-Cowdin, Roberta
AU - Torres, Mina
AU - Preuss, Michael H
AU - Loos, Ruth J F
AU - Zawistowski, Matthew
AU - Zöllner, Sebastian
AU - Lu, Zeyun
AU - Van Den Eeden, Stephen K
AU - Easton, Douglas F
AU - Ambs, Stefan
AU - Edwards, Todd L
AU - Mägi, Reedik
AU - Rebbeck, Timothy R
AU - Fritsche, Lars
AU - Chanock, Stephen J
AU - Berndt, Sonja I
AU - Wiklund, Fredrik
AU - Nakagawa, Hidewaki
AU - Witte, John S
AU - Gaziano, J Michael
AU - Justice, Amy C
AU - Mancuso, Nick
AU - Terao, Chikashi
AU - BioBank Japan Project
AU - Eeles, Rosalind A
AU - Kote-Jarai, Zsofia
AU - Madduri, Ravi K
AU - Conti, David V
AU - Haiman, Christopher A
N1 - © 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2023/12
Y1 - 2023/12
N2 - 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.
AB - 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.
KW - Humans
KW - Male
KW - Black People/genetics
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - Hispanic or Latino/genetics
KW - Polymorphism, Single Nucleotide
KW - Prostatic Neoplasms/genetics
KW - Risk Factors
KW - White People/genetics
KW - Asian People/genetics
U2 - 10.1038/s41588-023-01534-4
DO - 10.1038/s41588-023-01534-4
M3 - SCORING: Journal article
C2 - 37945903
VL - 55
SP - 2065
EP - 2074
JO - NAT GENET
JF - NAT GENET
SN - 1061-4036
IS - 12
ER -