撒哈拉以南非洲前列腺癌易感性的异质遗传结构。
Heterogeneous genetic architectures of prostate cancer susceptibility in sub-Saharan Africa.
发表日期：2024 Oct 02
作者：
Rohini Janivara, Wenlong C Chen, Ujani Hazra, Shakuntala Baichoo, Ilir Agalliu, Paidamoyo Kachambwa, Corrine N Simonti, Lyda M Brown, Saanika P Tambe, Michelle S Kim, Maxine Harlemon, Mohamed Jalloh, Dillon Muzondiwa, Daphne Naidoo, Olabode O Ajayi, Nana Yaa Snyper, Lamine Niang, Halimatou Diop, Medina Ndoye, James E Mensah, Afua O D Abrahams, Richard Biritwum, Andrew A Adjei, Akindele O Adebiyi, Olayiwola Shittu, Olufemi Ogunbiyi, Sikiru Adebayo, Maxwell M Nwegbu, Hafees O Ajibola, Olabode P Oluwole, Mustapha A Jamda, Audrey Pentz, Christopher A Haiman, Petrus V Spies, André van der Merwe, Michael B Cook, Stephen J Chanock, Sonja I Berndt, Stephen Watya, Alexander Lubwama, Mazvita Muchengeti, Sean Doherty, Natalie Smyth, David Lounsbury, Brian Fortier, Thomas E Rohan, Judith S Jacobson, Alfred I Neugut, Ann W Hsing, Alexander Gusev, Oseremen I Aisuodionoe-Shadrach, Maureen Joffe, Ben Adusei, Serigne M Gueye, Pedro W Fernandez, Jo McBride, Caroline Andrews, Lindsay N Petersen, Joseph Lachance, Timothy R Rebbeck
来源：
NATURE GENETICS
摘要：
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尚未得到充分研究。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血统特异性遗传结构和精细图谱疾病关联。 8q24.21、6q22.1 和 11q13.3 上的 15 个独立关联达到了全基因组显着性，其中包括 4 个新关联。有趣的是，多个先导关联是私人等位基因，这是由最近的突变和非洲之外的瓶颈产生的模式。这些非洲特有的等位基因产生比值比高于 2.4 的单倍型。我们发现，非洲各地前列腺癌的遗传结构各不相同，效应大小差异比等位基因频率差异对这种异质性的影响更大。群体遗传学分析表明，非洲前列腺癌协会很大程度上受中性进化的控制。总的来说，我们的研究结果强调了利用不同人群进行遗传学研究的实用性。© 2024。作者获得 Springer Nature America, Inc. 的独家许可。
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.© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.