A map of blood regulatory variation in South Africans enables GWAS interpretation
Functional genomics resources are critical for interpreting human genetic studies, but currently they are predominantly from European-ancestry individuals. Here we present the South African Blood Regulatory (SABR) resource, a map of blood regulatory variation that includes three South Eastern Bantu-speaking groups. Using paired whole-genome and blood transcriptome data from over 600 individuals, we map the genetic architecture of 40 blood cell traits derived from deconvolution analysis, as well as expression, splice and cell-type interaction quantitative trait loci. We comprehensively compare SABR to the Genotype Tissue Expression Project and characterize thousands of regulatory variants only observed in African-ancestry individuals. Finally, we demonstrate the increased utility of SABR for interpreting African-ancestry association studies by identifying putatively causal genes and molecular mechanisms through colocalization analysis of blood-relevant traits from the Pan-UK Biobank. Importantly, we make full SABR summary statistics publicly available to support the African genomics community.
Authors
- Lisa K. Micklesfield (ORCID: https://orcid.org/0000-0002-4994-0779)
- Solomon S R Choma
- Dhriti Sengupta (ORCID: https://orcid.org/0000-0001-6315-7804)
- F. Xavier Gómez‐Olivé (ORCID: https://orcid.org/0000-0002-4876-0848)
- Scott Hazelhurst (ORCID: https://orcid.org/0000-0002-0581-149X)
- Laura M. Yerges-Armstrong (ORCID: https://orcid.org/0000-0003-0006-5237)
- Melissa Hendershott (ORCID: https://orcid.org/0000-0002-4769-2548)
- Kathleen Kahn (ORCID: https://orcid.org/0000-0003-3339-3931)
- Ananyo Choudhury (ORCID: https://orcid.org/0000-0001-8225-9531)
- Mohd Anisul Karim (ORCID: https://orcid.org/0000-0003-2960-6017)
- Phelelani Thokozani Mpangase (ORCID: https://orcid.org/0000-0001-8280-8940)
- Stephane E. Castel (ORCID: https://orcid.org/0000-0002-0707-2133)
- Chodziwadziwa Kabudula (ORCID: https://orcid.org/0000-0002-5867-0336)
- Sarah LeBaron von Baeyer (ORCID: https://orcid.org/0009-0005-0056-6201)
- Reneilwe Given Mashaba (ORCID: https://orcid.org/0000-0001-6235-2325)
- Michèle Ramsay (ORCID: https://orcid.org/0000-0002-4156-4801)
- Erin E. Burke (ORCID: https://orcid.org/0000-0002-7559-4961)
- Kaja A. Wasik (ORCID: https://orcid.org/0009-0002-2789-0974)
- Furahini D Tluway
- Olivia Gray (ORCID: https://orcid.org/0000-0002-6585-9049)
- Natalie Smyth
- Sarah Kaewert
- Khanh-Dung H. Nguyen
- Anne-Katrin Emde
Institutions
- South African Medical Research Council (ZA)
- University of the Witwatersrand (ZA)
- Varian Medical Systems (United States) (US)
- University of Limpopo (ZA)
Publication Details
- Journal
- Nature Genetics
- Published
- 2025-06-11
- DOI
- https://doi.org/10.1038/s41588-025-02223-0
- Citations
- 4
- Primary Topic
- Genetic Associations and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 7.27
Funders
- Wellcome Trust
- Department of Science and Innovation, South Africa
- National Research Foundation
- South African Medical Research Council
- Department of Science and Technology, Ministry of Science and Technology, India
- National Institutes of Health
- Medical Research Council
- National Heart, Lung, and Blood Institute