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 | |
Publication status | Published - Dec 2023 |
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Publisher Copyright:© 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.
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In: Nature Genetics, Vol. 55, No. 12, 12.2023, p. 2065-2074.
Research output: Contribution to journal › Article › Academic › peer-review
TY - JOUR
T1 - Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
AU - Wang, Anqi
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AU - Razack, Azad
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AU - Usmani, Nawaid
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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 - Eeles, Rosalind A.
AU - Kote-Jarai, Zsofia
AU - Madduri, Ravi K.
AU - Conti, David V.
AU - Haiman, Christopher A.
N1 - Publisher Copyright: © 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.
UR - http://www.scopus.com/inward/record.url?scp=85176259299&partnerID=8YFLogxK
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 -