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

by Vega, Ana , Hamilton, Robert J. , Wu, Yudong , Mitev, Vanio , Terao, Chikashi , Mante, Sunny , Witte, John S. , Sun, Zan , Razack, Azad , Zhao, Shan-Chao , Carpten, John , Darst, Burcu F. , Chen, Fei , Chen, Xuechen , Hamdy, Freddie C. , Rentsch, Christopher T. , Nakagawa, Hidewaki , Van den Broeck, Thomas , Parent, Marie-Élise , De Ruyck, Kim , Wolk, Alicja , Clements, Judith A. , Mucci, Lorelei A. , Drake, Bettina F. , Gueye, Serigne M. , Darkwa-Abrahams, Afua , Sheng, Xin , Pilie, Patrick , Ingles, Sue A. , Giles, Graham G. , Berndt, Sonja I. , Wokolorczyk, Dominika , Thibodeau, Stephen N. , Kerns, Sarah L. , Kittles, Rick A. , Zhang, Hong-Wei , Neslund-Dudas, Christine M. , Amodu, Olukemi , Sahimi, Ali , Blanchet, Pascal , Cancel-Tassin, Geraldine , Lubwama, Alexander , Lori, Adriana , Park, Jong Y. , Fachal, Laura , Stanford, Janet L. , Kaneva, Radka , Lachance, Joseph , Bensen, Jeannette T. , Conti, David V. , Van Den Eeden, Stephen K. , Plym, Anna , Ostrander, Elaine A. , McDonnell, Shannon K. , Haiman, Christopher A. , Nielsen, Sune F. , Shittu, Olayiwola , Key, Tim J. , Ito, Shuji , Lubinski, Jan , Ghoussaini, Maya , Rebbeck, Timothy R. , Lu, Yong-Jie , Ding, Yu

in 45/43 / 631/208/205/2138 / 692/308/2056 / 692/699/67/589/466 / 692/700/459/1748 / Agriculture / Androgens / Animal Genetics and Genomics / Asian People - genetics / Biomedical and Life Sciences / Biomedicine / Black People - genetics / Cancer Research / Gene expression / Gene Function / Genetic diversity / Genetic Predisposition to Disease / Genome-wide association studies / Genome-Wide Association Study / Genomes / Health risks / Hispanic or Latino - genetics / Hispanic people / Human Genetics / Humans / Kinases / Letter / Life Sciences / Male / Meta-analysis / Polymorphism, Single Nucleotide / Population studies / Populations / Prostate cancer / Prostatic Neoplasms - genetics / Risk / Risk Factors / Transcription factors / White People - genetics

2023

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

2023

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2023

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Journal Article

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

Vega, Ana,

Hamilton, Robert J.,

Wu, Yudong,

Mitev, Vanio,

Terao, Chikashi,

Mante, Sunny,

Witte, John S.,

Sun, Zan,

Razack, Azad,

Zhao, Shan-Chao,

Carpten, John,

Darst, Burcu F.,

Chen, Fei,

Chen, Xuechen,

Hamdy, Freddie C.,

Rentsch, Christopher T.,

Nakagawa, Hidewaki,

Van den Broeck, Thomas,

Parent, Marie-Élise,

De Ruyck, Kim,

Wolk, Alicja,

Clements, Judith A.,

Mucci, Lorelei A.,

Drake, Bettina F.,

Gueye, Serigne M.,

Darkwa-Abrahams, Afua,

Sheng, Xin,

Pilie, Patrick,

Ingles, Sue A.,

Giles, Graham G.,

Berndt, Sonja I.,

Wokolorczyk, Dominika,

Thibodeau, Stephen N.,

Kerns, Sarah L.,

Kittles, Rick A.,

Zhang, Hong-Wei,

Neslund-Dudas, Christine M.,

Amodu, Olukemi,

Sahimi, Ali,

Blanchet, Pascal,

Cancel-Tassin, Geraldine,

Lubwama, Alexander,

Lori, Adriana,

Park, Jong Y.,

Fachal, Laura,

Stanford, Janet L.,

Kaneva, Radka,

Lachance, Joseph,

Bensen, Jeannette T.,

Conti, David V.,

Van Den Eeden, Stephen K.,

Plym, Anna,

Ostrander, Elaine A.,

McDonnell, Shannon K.,

Haiman, Christopher A.,

Nielsen, Sune F.,

Shittu, Olayiwola,

Key, Tim J.,

Ito, Shuji,

Lubinski, Jan,

Ghoussaini, Maya,

Rebbeck, Timothy R.,

Lu, Yong-Jie,

Ding, Yu

2023

Overview

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. A multi-ancestry genome-wide association study of prostate cancer performed in 156,319 cases and 788,443 controls identifies 187 novel risk variants associated with the disease. Genetic risk scores associated with overall risk, and risk of aggressive disease in men of African ancestry.

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Nature Publishing Group US,Nature Publishing Group

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