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 - Nordestgaard, Borge G
AU - Nielsen, Sune F
AU - Weischer, Maren
AU - Bojesen, Stig E
AU - Røder, Andreas
AU - Stroomberg, Hein V
AU - BioBank Japan Project
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 - 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
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 - Journal article
C2 - 37945903
SN - 1061-4036
VL - 55
SP - 2065
EP - 2074
JO - Nature Genetics
JF - Nature Genetics
IS - 12
ER -