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

Title: Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
Authors: 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; Project, Biobank Japan; 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; Cho, K; Mcmahon, BH; Neal, DE; Donovan, JL; Hamdy, FC; Travis, RC; Key, TJ; Hunter, DJ
Publisher Information: Springer Nature
Publication Year: 2024
Collection: Oxford University Research Archive (ORA)
Description: 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.
Document Type: article in journal/newspaper
Language: English
DOI: 10.1038/s41588-023-01534-4
Availability: https://doi.org/10.1038/s41588-023-01534-4; https://ora.ox.ac.uk/objects/uuid:25b697a7-8ab7-4a9a-ba02-3fffe6dbf5b2
Rights: info:eu-repo/semantics/openAccess
Accession Number: edsbas.CE5157D
Database: BASE