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
{"title":"撒哈拉以南非洲地区前列腺癌易感性的异质遗传结构","authors":"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","doi":"10.1038/s41588-024-01931-3","DOIUrl":null,"url":null,"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. Genome-wide association analyses of prostate cancer in men from sub-Saharan Africa identify population-specific risk variants and regional differences in effect sizes. Founder effects contribute to continental differences in the genetic architecture of prostate cancer.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"56 10","pages":"2093-2103"},"PeriodicalIF":31.7000,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Heterogeneous genetic architectures of prostate cancer susceptibility in sub-Saharan Africa\",\"authors\":\"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\",\"doi\":\"10.1038/s41588-024-01931-3\",\"DOIUrl\":null,\"url\":null,\"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. 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Heterogeneous genetic architectures of prostate cancer susceptibility in sub-Saharan Africa
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. Genome-wide association analyses of prostate cancer in men from sub-Saharan Africa identify population-specific risk variants and regional differences in effect sizes. Founder effects contribute to continental differences in the genetic architecture of prostate cancer.
期刊介绍:
Nature Genetics publishes the very highest quality research in genetics. It encompasses genetic and functional genomic studies on human and plant traits and on other model organisms. Current emphasis is on the genetic basis for common and complex diseases and on the functional mechanism, architecture and evolution of gene networks, studied by experimental perturbation.
Integrative genetic topics comprise, but are not limited to:
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-Molecular analysis of simple and complex genetic traits
-Cancer genetics
-Agricultural genomics
-Developmental genetics
-Regulatory variation in gene expression
-Strategies and technologies for extracting function from genomic data
-Pharmacological genomics
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