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

Document Type

Article

Publication Date

12-1-2023

Publication Title

Nature genetics

Keywords

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

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.

Medical Subject Headings

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

PubMed ID

37945903

Volume

55

Issue

12

First Page

2065

Last Page

2074

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