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

Authors：Wang, Anqi; Shen, Jiayi; Rodriguez, Alex A.; Saunders, Edward J.; Chen, Fei; Janivara, Rohini; Darst, Burcu F.; Sheng, Xin; Xu, Yili; Chou, Alisha J.; Benlloch, Sara; Dadaev, Tokhir; Brook, Mark N.; Plym, Anna; Sahimi, Ali; Hoffman, Thomas J.; Takahashi, Atushi; Matsuda, Koichi; Momozawa, Yukihide; Fujita, Masashi; Laisk, Triin; Figueredo, Jessica; Muir, Kenneth; Ito, Shuji; Liu, Xiaoxi; Uchio, Yuji; Kubo, Michiaki; Kamatani, Yoichiro; Lophatananon, Artitaya; Wan, Peggy; Andrews, Caroline

Source：Nature Genetics, 2023, 55(12): 2065-+.

DOI：10.1038/s41588-023-01534-4

• SUSCEPTIBILITY LOCI
• BREAST-CANCER
• ASSOCIATION
• COMMON
• METAANALYSIS
• AFRICAN
• IDENTIFICATION
• CONSORTIUM
• EXPRESSION
• RESOURCE

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.