In this first whole-exome sequencing study of prostate cancer, our findings do not provide strong support for the hypothesis that NS coding variants down to 0.5–1.0% frequency have large effects on prostate cancer risk in men of African ancestry. We did not observe exome-wide significant associations (after correcting for multiple hypothesis testing) in single variant or gene-level testing in the overall case–control or case–case analyses of disease aggressiveness. In gene-level testing, the two most significant genes were C1orf100 ( P = 2.2 × 10 −4) and GORAB ( P = 2.3 × 10 −4). ![]() ![]() ![]() To explore the contribution of both rare and common variation in coding regions to prostate cancer risk, we sequenced the exomes of 2165 prostate cancer cases and 2034 controls of African ancestry at a mean coverage of 10.1×. Epidemiologic evidence supports a large heritable contribution to prostate cancer, with over 100 susceptibility loci identified to date that can explain ∼33% of the familial risk. ![]() Prostate cancer is the most common non-skin cancer in males, with a ∼1.5–2-fold higher incidence in African American men when compared with whites.
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