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Low and differential polygenic score generalizability among African populations due largely to genetic diversity
African populations are vastly underrepresented in genetic studies but have the most genetic variation and face wide-ranging environmental exposures globally. Because systematic evaluations of genetic prediction had not yet been conducted in ancestries that span African diversity, we calculated poly...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9982687/ https://www.ncbi.nlm.nih.gov/pubmed/36873096 http://dx.doi.org/10.1016/j.xhgg.2023.100184 |
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author | Majara, Lerato Kalungi, Allan Koen, Nastassja Tsuo, Kristin Wang, Ying Gupta, Rahul Nkambule, Lethukuthula L. Zar, Heather Stein, Dan J. Kinyanda, Eugene Atkinson, Elizabeth G. Martin, Alicia R. |
author_facet | Majara, Lerato Kalungi, Allan Koen, Nastassja Tsuo, Kristin Wang, Ying Gupta, Rahul Nkambule, Lethukuthula L. Zar, Heather Stein, Dan J. Kinyanda, Eugene Atkinson, Elizabeth G. Martin, Alicia R. |
author_sort | Majara, Lerato |
collection | PubMed |
description | African populations are vastly underrepresented in genetic studies but have the most genetic variation and face wide-ranging environmental exposures globally. Because systematic evaluations of genetic prediction had not yet been conducted in ancestries that span African diversity, we calculated polygenic risk scores (PRSs) in simulations across Africa and in empirical data from South Africa, Uganda, and the United Kingdom to better understand the generalizability of genetic studies. PRS accuracy improves with ancestry-matched discovery cohorts more than from ancestry-mismatched studies. Within ancestrally and ethnically diverse South African individuals, we find that PRS accuracy is low for all traits but varies across groups. Differences in African ancestries contribute more to variability in PRS accuracy than other large cohort differences considered between individuals in the United Kingdom versus Uganda. We computed PRS in African ancestry populations using existing European-only versus ancestrally diverse genetic studies; the increased diversity produced the largest accuracy gains for hemoglobin concentration and white blood cell count, reflecting large-effect ancestry-enriched variants in genes known to influence sickle cell anemia and the allergic response, respectively. Differences in PRS accuracy across African ancestries originating from diverse regions are as large as across out-of-Africa continental ancestries, requiring commensurate nuance. |
format | Online Article Text |
id | pubmed-9982687 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-99826872023-03-04 Low and differential polygenic score generalizability among African populations due largely to genetic diversity Majara, Lerato Kalungi, Allan Koen, Nastassja Tsuo, Kristin Wang, Ying Gupta, Rahul Nkambule, Lethukuthula L. Zar, Heather Stein, Dan J. Kinyanda, Eugene Atkinson, Elizabeth G. Martin, Alicia R. HGG Adv Article African populations are vastly underrepresented in genetic studies but have the most genetic variation and face wide-ranging environmental exposures globally. Because systematic evaluations of genetic prediction had not yet been conducted in ancestries that span African diversity, we calculated polygenic risk scores (PRSs) in simulations across Africa and in empirical data from South Africa, Uganda, and the United Kingdom to better understand the generalizability of genetic studies. PRS accuracy improves with ancestry-matched discovery cohorts more than from ancestry-mismatched studies. Within ancestrally and ethnically diverse South African individuals, we find that PRS accuracy is low for all traits but varies across groups. Differences in African ancestries contribute more to variability in PRS accuracy than other large cohort differences considered between individuals in the United Kingdom versus Uganda. We computed PRS in African ancestry populations using existing European-only versus ancestrally diverse genetic studies; the increased diversity produced the largest accuracy gains for hemoglobin concentration and white blood cell count, reflecting large-effect ancestry-enriched variants in genes known to influence sickle cell anemia and the allergic response, respectively. Differences in PRS accuracy across African ancestries originating from diverse regions are as large as across out-of-Africa continental ancestries, requiring commensurate nuance. Elsevier 2023-02-13 /pmc/articles/PMC9982687/ /pubmed/36873096 http://dx.doi.org/10.1016/j.xhgg.2023.100184 Text en © 2023 The Authors https://creativecommons.org/licenses/by/4.0/This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Majara, Lerato Kalungi, Allan Koen, Nastassja Tsuo, Kristin Wang, Ying Gupta, Rahul Nkambule, Lethukuthula L. Zar, Heather Stein, Dan J. Kinyanda, Eugene Atkinson, Elizabeth G. Martin, Alicia R. Low and differential polygenic score generalizability among African populations due largely to genetic diversity |
title | Low and differential polygenic score generalizability among African populations due largely to genetic diversity |
title_full | Low and differential polygenic score generalizability among African populations due largely to genetic diversity |
title_fullStr | Low and differential polygenic score generalizability among African populations due largely to genetic diversity |
title_full_unstemmed | Low and differential polygenic score generalizability among African populations due largely to genetic diversity |
title_short | Low and differential polygenic score generalizability among African populations due largely to genetic diversity |
title_sort | low and differential polygenic score generalizability among african populations due largely to genetic diversity |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9982687/ https://www.ncbi.nlm.nih.gov/pubmed/36873096 http://dx.doi.org/10.1016/j.xhgg.2023.100184 |
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