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Table S3 from A Custom Genotyping Array Reveals Population-Level Heterogeneity for the Genetic Risks of Prostate Cancer and Other Cancers in Africa

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posted on 2023-03-31, 03:02 authored by Maxine Harlemon, Olabode Ajayi, Paidamoyo Kachambwa, Michelle S. Kim, Corinne N. Simonti, Melanie H. Quiver, Desiree C. Petersen, Anuradha Mittal, Pedro W. Fernandez, Ann W. Hsing, Shakuntala Baichoo, Ilir Agalliu, Mohamed Jalloh, Serigne M. Gueye, Nana Yaa F. Snyper, Ben Adusei, James E. Mensah, Afua O.D. Abrahams, Akindele O. Adebiyi, Akin T. Orunmuyi, Oseremen I. Aisuodionoe-Shadrach, Maxwell M. Nwegbu, Maureen Joffe, Wenlong C. Chen, Hayley Irusen, Alfred I. Neugut, Yuri Quintana, Moleboheng Seutloali, Mayowa B. Fadipe, Christopher Warren, Marcos H. Woehrmann, Peng Zhang, Chrissie M. Ongaco, Michelle Mawhinney, Jo McBride, Caroline V. Andrews, Marcia Adams, Elizabeth Pugh, Timothy R. Rebbeck, Lindsay N. Petersen, Joseph Lachance

Markers used in PRS calculations. This list includes all markers from the Schumacher et al. 2018 CaP PRS (10) as well as proxy markers that are found on the MADCaP Array. Chromosome and positions (build hg38) listed here are for MADCaP markers used in PRS calculations. Allele frequencies and PBS scores are also included for the 139 CaP markers used in MADCaP PRS calculations. Numbers of markers on each genotyping array within 50kb of CaP-associated loci from Schumacher et al. 2018 are also included here.

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NIH

NCI

School of Biological Sciences at Georgia Institute of Technology

Integrated Cancer Research Center at Georgia Institute of Technology

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ARTICLE ABSTRACT

Although prostate cancer is the leading cause of cancer mortality for African men, the vast majority of known disease associations have been detected in European study cohorts. Furthermore, most genome-wide association studies have used genotyping arrays that are hindered by SNP ascertainment bias. To overcome these disparities in genomic medicine, the Men of African Descent and Carcinoma of the Prostate (MADCaP) Network has developed a genotyping array that is optimized for African populations. The MADCaP Array contains more than 1.5 million markers and an imputation backbone that successfully tags over 94% of common genetic variants in African populations. This array also has a high density of markers in genomic regions associated with cancer susceptibility, including 8q24. We assessed the effectiveness of the MADCaP Array by genotyping 399 prostate cancer cases and 403 controls from seven urban study sites in sub-Saharan Africa. Samples from Ghana and Nigeria clustered together, whereas samples from Senegal and South Africa yielded distinct ancestry clusters. Using the MADCaP array, we identified cancer-associated loci that have large allele frequency differences across African populations. Polygenic risk scores for prostate cancer were higher in Nigeria than in Senegal. In summary, individual and population-level differences in prostate cancer risk were revealed using a novel genotyping array. This study presents an Africa-specific genotyping array, which enables investigators to identify novel disease associations and to fine-map genetic loci that are associated with prostate and other cancers.

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