Publication Type: Journal Article
Authors: Janivara, Rohini; Chen, Wenlong C; Hazra, Ujani; Baichoo, Shakuntala; Agalliu, Ilir; Kachambwa, Paidamoyo; Simonti, Corrine N; Brown, Lyda M; Tambe, Saanika P; Kim, Michelle S; Harlemon, Maxine; Jalloh, Mohamed; Muzondiwa, Dillon; Naidoo, Daphne; Ajayi, Olabode O; Snyper, Nana Yaa; Niang, Lamine; Diop, Halimatou; Ndoye, Medina; Mensah, James E; Abrahams, Afua O D; Biritwum, Richard; Adjei, Andrew A; Adebiyi, Akindele O; Shittu, Olayiwola; Ogunbiyi, Olufemi; Adebayo, Sikiru; Nwegbu, Maxwell M; Ajibola, Hafees O; Oluwole, Olabode P; Jamda, Mustapha A; Pentz, Audrey; Haiman, Christopher A; Spies, Petrus V; van der Merwe, André; Cook, Michael B; Chanock, Stephen J; Berndt, Sonja I; Watya, Stephen; Lubwama, Alexander; Muchengeti, Mazvita; Doherty, Sean; Smyth, Natalie; Lounsbury, David; Fortier, Brian; Rohan, Thomas E; Jacobson, Judith S; Neugut, Alfred I; Hsing, Ann W; Gusev, Alexander; Aisuodionoe-Shadrach, Oseremen I; Joffe, Maureen; Adusei, Ben; Gueye, Serigne M; Fernandez, Pedro W; McBride, Jo; Andrews, Caroline; Petersen, Lindsay N; Lachance, Joseph; Rebbeck, Timothy R
Year of Publication: 2024
Journal: Nat Genet
Volume: 56
Issue: 10
Pagination: 2093-2103
Date Published: 2024 Oct
Publication Language: eng
ISSN: 1546-1718
Keywords: Africa South of the Sahara, Alleles, Black People, Case-Control Studies, Gene Frequency, Genetic Predisposition to Disease, Genetics, Population, Genome-Wide Association Study, Haplotypes, Humans, Male, Polymorphism, Single Nucleotide, Prostatic Neoplasms
Abstract: 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.
DOI: https://doi.org/10.1038/s41588-024-01931-3
Alternate Journal: Nat Genet
