| Title: | Low and differential polygenic score generalizability among African populations due largely to genetic diversity |
| Journal: | Human Genetics and Genomics Advances |
| Published: | 13 Feb 2023 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/36873096/ |
| DOI: | https://doi.org/10.1016/j.xhgg.2023.100184 |
Publication 11080
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Abstract
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.</p>
12 Authors
- Lerato Majara
- Allan Kalungi
- Nastassja Koen
- Kristin Tsuo
- Ying Wang
- Rahul Gupta
- Lethukuthula L. Nkambule
- Heather Zar
- Dan J. Stein
- Eugene Kinyanda
- Elizabeth G. Atkinson
- Alicia R. Martin
1 Application
| Application ID | Title |
|---|---|
| 31063 | Methodological extensions to estimate genetic heritability and shared risk factors for phenotypes of the UK Biobank |
Enabling scientific discoveries that improve human health