Men of African descent have the highest prostate cancer incidence and mortality rates, yet the genetic basis of prostate cancer in African men has been understudied. We used genomic data from 3,963 cases and 3,509 controls from Ghana, Nigeria, Senegal, South Africa and Uganda to infer ancestry-specific genetic architectures and fine-map disease associations. Fifteen independent associations at 8q24.21, 6q22.1 and 11q13.3 reached genome-wide significance, including four new associations. Intriguingly, multiple lead associations are private alleles, a pattern arising from recent mutations and the out-of-Africa bottleneck. These African-specific alleles contribute to haplotypes with odds ratios above 2.4. We found that the genetic architecture of prostate cancer differs across Africa, with effect size differences contributing more to this heterogeneity than allele frequency differences. Population genetic analyses reveal that African prostate cancer associations are largely governed by neutral evolution. Collectively, our findings emphasize the utility of conducting genetic studies that use diverse populations.

非洲裔男性的前列腺癌发病率和死亡率最高，但非洲男性前列腺癌的遗传基础研究不足。我们使用来自加纳、尼日利亚、塞内加尔、南非和乌干达的 3,963 例病例和 3,509 例对照的基因组数据来推断祖先特异性遗传结构并精细绘制疾病关联。8q24.21、6q22.1 和 11q13.3 的 15 个独立关联达到全基因组意义，包括 4 个新关联。有趣的是，多个先导化合物关联是私有等位基因，这种模式是由最近的突变和非洲以外的瓶颈引起的。这些非洲特异性等位基因有助于比值比高于 2.4 的单倍型。我们发现前列腺癌的遗传结构在非洲各地有所不同，效应大小差异比等位基因频率差异更能造成这种异质性。群体遗传分析表明，非洲前列腺癌关联在很大程度上受中性进化的支配。总的来说，我们的研究结果强调了使用不同人群进行遗传研究的效用。