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

• Verfasst von: Wang, Anqi [VerfasserIn]
• Verfasst von: Brenner, Hermann [VerfasserIn]
• Verfasst von: Chen, Xuechen [VerfasserIn]
• Titel: Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
• Titelzusatz: letter
• Verf.angabe: Anqi Wang, Hermann Brenner, Xuechen Chen [und 288 weitere]
• E-Jahr: 2023
• Jahr: 09 November 2023
• Umfang: 10 S.
• Fussnoten: Gesehen am 17.07.2024
• Titel Quelle: Enthalten in: Nature genetics
• Ort Quelle: London : Macmillan Publishers Limited, part of Springer Nature, 1992
• Jahr Quelle: 2023
• Band/Heft Quelle: 55(2023), 12, Seite 2065-2074
• ISSN Quelle: 1546-1718
• DOI: doi:10.1038/s41588-023-01534-4
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Genetics research
• Sach-SW: Genome-wide association studies
• Sach-SW: Preventive medicine
• Sach-SW: Prostate cancer
• K10plus-PPN: 1895627613

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.