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

Anqi Wang; Jiayi Shen; Alex A Rodriguez; Edward J Saunders; Fei Chen; Rohini Janivara; Burcu F Darst; Xin Sheng; Yili Xu; Alisha J Chou; Sara Benlloch; Tokhir Dadaev; Mark N Brook; Anna Plym; Ali Sahimi; Thomas J Hoffman; Atushi Takahashi; Koichi Matsuda; Yukihide Momozawa; Masashi Fujita; Triin Laisk; Jéssica Figuerêdo; Kenneth Muir; Shuji Ito; Xiaoxi Liu; Yuji Uchio; Michiaki Kubo; Yoichiro Kamatani; Artitaya Lophatananon; Peggy Wan; Caroline Andrews; Adriana Lori; Parichoy P Choudhury; Johanna Schleutker; Teuvo L J Tammela; Csilla Sipeky; Anssi Auvinen; Graham G Giles; Melissa C Southey; Robert J MacInnis; Cezary Cybulski; Dominika Wokolorczyk; Jan Lubinski; Christopher T Rentsch; Borge G Nordestgaard; Sune F Nielsen; Maren Weischer; Stig E Bojesen; Andreas Røder; Hein V Stroomberg; BioBank Japan Project

doi:10.1038/s41588-023-01534-4

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

Anqi Wang, Jiayi Shen, Alex A Rodriguez, Edward J Saunders, Fei Chen, Rohini Janivara, Burcu F Darst, Xin Sheng, Yili Xu, Alisha J Chou, Sara Benlloch, Tokhir Dadaev, Mark N Brook, Anna Plym, Ali Sahimi, Thomas J Hoffman, Atushi Takahashi, Koichi Matsuda, Yukihide Momozawa, Masashi FujitaTriin Laisk, Jéssica Figuerêdo, Kenneth Muir, Shuji Ito, Xiaoxi Liu, Yuji Uchio, Michiaki Kubo, Yoichiro Kamatani, Artitaya Lophatananon, Peggy Wan, Caroline Andrews, Adriana Lori, Parichoy P Choudhury, Johanna Schleutker, Teuvo L J Tammela, Csilla Sipeky, Anssi Auvinen, Graham G Giles, Melissa C Southey, Robert J MacInnis, Cezary Cybulski, Dominika Wokolorczyk, Jan Lubinski, Christopher T Rentsch, Borge G Nordestgaard, Sune F Nielsen, Maren Weischer, Stig E Bojesen, Andreas Røder, Hein V Stroomberg, BioBank Japan Project

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
Journal	Nature Genetics
Volume	55
Issue number	12
Pages (from-to)	2065-2074
Number of pages	10
ISSN	1061-4036
DOIs	https://doi.org/10.1038/s41588-023-01534-4
Publication status	Published - Dec 2023

Keywords

Asian People/genetics
Black People/genetics
Genetic Predisposition to Disease
Genome-Wide Association Study
Hispanic or Latino/genetics
Humans
Male
Polymorphism, Single Nucleotide
Prostatic Neoplasms/genetics
Risk Factors
White People/genetics

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Wang, A., Shen, J., Rodriguez, A. A., Saunders, E. J., Chen, F., Janivara, R., Darst, B. F., Sheng, X., Xu, Y., Chou, A. J., Benlloch, S., Dadaev, T., Brook, M. N., Plym, A., Sahimi, A., Hoffman, T. J., Takahashi, A., Matsuda, K., Momozawa, Y., ... BioBank Japan Project (2023). Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants. Nature Genetics, 55(12), 2065-2074. https://doi.org/10.1038/s41588-023-01534-4

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, 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, Nordestgaard, BG , Nielsen, SF, Weischer, M, Bojesen, SE , Røder, A , Stroomberg, HV & BioBank Japan Project 2023, 'Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants', Nature Genetics, vol. 55, no. 12, pp. 2065-2074. https://doi.org/10.1038/s41588-023-01534-4

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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.",

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author = "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 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 Nordestgaard, \{Borge G\} and Nielsen, \{Sune F\} and Maren Weischer and Bojesen, \{Stig E\} and Andreas R{\o}der and Stroomberg, \{Hein V\} and \{BioBank Japan Project\}",

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

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AU - Chen, Fei

AU - Janivara, Rohini

AU - Darst, Burcu F

AU - Sheng, Xin

AU - Xu, Yili

AU - Chou, Alisha J

AU - Benlloch, Sara

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AU - Brook, Mark N

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AU - Sahimi, Ali

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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

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AU - Nordestgaard, Borge G

AU - Nielsen, Sune F

AU - Weischer, Maren

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AU - BioBank Japan Project

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KW - Asian People/genetics

KW - Black People/genetics

KW - Genetic Predisposition to Disease

KW - Genome-Wide Association Study

KW - Hispanic or Latino/genetics

KW - Humans

KW - Male

KW - Polymorphism, Single Nucleotide

KW - Prostatic Neoplasms/genetics

KW - Risk Factors

KW - White People/genetics

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SN - 1061-4036

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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

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Keywords

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