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

The Biobank Japan Project; Anqi Wang; Jiayi Shen; Alex A. Rodriguez; Edward J. Saunders; Fei Chen; Rohini Janivara; Burcu F. Darst; Xin Sheng; Yili Xu; Jyotsna Batra; Christopher A Haiman

doi:10.1038/s41588-023-01534-4

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

The Biobank Japan Project
, Anqi Wang
, Jiayi Shen
, Alex A. Rodriguez
, Edward J. Saunders
, Fei Chen
, Rohini Janivara
, Burcu F. Darst
, Xin Sheng
, Yili Xu
, Jyotsna Batra
, Christopher A Haiman^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Research › peer-review

99 Citations (Scopus)

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.

Original language	English
Pages (from-to)	2065-2074
Number of pages	10
Journal	Nature Genetics
Volume	55
Issue number	12
DOIs	https://doi.org/10.1038/s41588-023-01534-4
Publication status	Published - 1 Dec 2023
Externally published	Yes

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SDG 3 Good Health and Well-being

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10.1038/s41588-023-01534-4

Cite this

@article{3d6d80d91d4a4ddbacd364217dd78522,

title = "Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants",

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.",

author = "\{The Biobank Japan Project\} and Anqi Wang and Jiayi Shen and Rodriguez, \{Alex A.\} and Saunders, \{Edward J.\} and Fei Chen and Rohini Janivara and Darst, \{Burcu F.\} and Xin Sheng and Yili Xu and Chou, \{Alisha J.\} and Sara Benlloch and Tokhir Dadaev and Brook, \{Mark N.\} and Anna Plym and Ali Sahimi and Hoffman, \{Thomas J.\} and Atushi Takahashi and Koichi Matsuda and Yukihide Momozawa and Masashi Fujita and Triin Laisk and J{\'e}ssica Figuer{\^e}do and Kenneth Muir and Shuji Ito and Xiaoxi Liu and Yuji Yamanashi and Yoichi Furukawa and Takayuki Morisaki and Yoshinori Murakami and Kaori Muto and Akiko Nagai and Wataru Obara and Ken Yamaji and Kazuhisa Takahashi and Satoshi Asai and Yasuo Takahashi and Takao Suzuki and Nobuaki Sinozaki and Hiroki Yamaguchi and Shiro Minami and Shigeo Murayama and Kozo Yoshimori and Satoshi Nagayama and Daisuke Obata and Masahiko Higashiyama and Akihide Masumoto and Yukihiro Koretsune and Yuji Uchio and Michiaki Kubo and Yoichiro Kamatani and Artitaya Lophatananon and Peggy Wan and Caroline Andrews and Adriana Lori and Choudhury, \{Parichoy P.\} and Johanna Schleutker and Tammela, \{Teuvo L.J.\} and Csilla Sipeky and Anssi Auvinen and Giles, \{Graham G.\} and Southey, \{Melissa C.\} and MacInnis, \{Robert J.\} and Cezary Cybulski and Dominika Wokolorczyk and Jan Lubinski and Rentsch, \{Christopher T.\} and Kelly Cho and Mcmahon, \{Benjamin H.\} and Neal, \{David E.\} and Donovan, \{Jenny L.\} and Hamdy, \{Freddie C.\} and Martin, \{Richard M.\} and Nordestgaard, \{Borge G.\} and Nielsen, \{Sune F.\} and Maren Weischer and Bojesen, \{Stig E.\} and Andreas R{\o}der and Stroomberg, \{Hein V.\} and Jyotsna Batra and Suzanne Chambers and Lisa Horvath and Clements, \{Judith A.\} and Wayne Tilly and Risbridger, \{Gail P.\} and Henrik Gronberg and Markus Aly and Robert Szulkin and Martin Eklund and Tobias Nordstrom and Nora Pashayan and Dunning, \{Alison M.\} and Maya Ghoussaini and Travis, \{Ruth C.\} and Key, \{Tim J.\} and Elio Riboli and Park, \{Jong Y.\} and Sellers, \{Thomas A.\} and Lin, \{Hui Yi\} and Demetrius Albanes and Stephanie Weinstein and Haiman, \{Christopher A\}",

year = "2023",

month = dec,

day = "1",

doi = "10.1038/s41588-023-01534-4",

language = "English",

volume = "55",

pages = "2065--2074",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "12",

}

TY - JOUR

T1 - Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants

AU - The Biobank Japan Project

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 - Yamanashi, Yuji

AU - Furukawa, Yoichi

AU - Morisaki, Takayuki

AU - Murakami, Yoshinori

AU - Muto, Kaori

AU - Nagai, Akiko

AU - Obara, Wataru

AU - Yamaji, Ken

AU - Takahashi, Kazuhisa

AU - Asai, Satoshi

AU - Takahashi, Yasuo

AU - Suzuki, Takao

AU - Sinozaki, Nobuaki

AU - Yamaguchi, Hiroki

AU - Minami, Shiro

AU - Murayama, Shigeo

AU - Yoshimori, Kozo

AU - Nagayama, Satoshi

AU - Obata, Daisuke

AU - Higashiyama, Masahiko

AU - Masumoto, Akihide

AU - Koretsune, Yukihiro

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 - Haiman, Christopher A

PY - 2023/12/1

Y1 - 2023/12/1

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.

UR - https://www.scopus.com/pages/publications/85176259299

U2 - 10.1038/s41588-023-01534-4

DO - 10.1038/s41588-023-01534-4

M3 - Article

C2 - 37945903

AN - SCOPUS:85176259299

SN - 1061-4036

VL - 55

SP - 2065

EP - 2074

JO - Nature Genetics

JF - Nature Genetics

IS - 12

ER -

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

Abstract

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