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Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci
journal contribution
posted on 2023-05-19, 19:23 authored by Schumacher, FR, Al Olama, AA, Berndt, SI, Benlloch, S, Ahmed, M, Liesel FitzgeraldLiesel Fitzgerald, Eeles, RAGenome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P < 5.0 × 10-8) with PrCa and one locus significantly associated with early-onset PrCa (≤55 years). Our findings include missense variants rs1800057 (odds ratio (OR) = 1.16; P = 8.2 × 10-9; G>C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 × 10-9; T>G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95% confidence interval (CI): 2.55-2.82) and first percentile (relative risk = 5.71; 95% CI: 5.04-6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa.
History
Publication title
Nature GeneticsVolume
50Issue
7Pagination
928-936ISSN
1061-4036Department/School
Menzies Institute for Medical ResearchPublisher
Nature Publishing GroupPlace of publication
345 Park Ave South, New York, USA, Ny, 10010-1707Rights statement
© 2018 Nature America Inc., part of Springer NatureRepository Status
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