Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants.
Wang A, Shen J, Rodriguez AA et al.
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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.
122,188 European ancestry cases, 604,640 European ancestry controls, 19,391 African American or Afro-Caribbean cases, 61,608 African American or Afro-Caribbean controls, 10,809 East Asian ancestry cases, 95,790 East Asian ancestry controls, 3,931 Hispanic or Latin American cases, 26,405 Hispanic or Latin American controls
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