New resource illuminates gene activity in African populations
- Wits University
First-of-its-kind dataset helps us understand why people from genetic backgrounds may be more vulnerable to certain diseases.
The newly launched South African Blood Regulatory (SABR) dataset reveals how genetic variation influences blood traits and gene activity in African populations, providing crucial insights into diseases like diabetes and heart disease.
This means researchers can now use the resource to better predict who is at risk, why specific populations respond differently to treatments, and how to develop more effective, tailored interventions.
With African populations historically underrepresented in genomic research, SABR marks a significant step toward more inclusive and more accurate precision medicine.
“SABR is a prized resource in that it connects genetic variation to gene activity, revealing how certain variants increase or decrease the expression of key genes. Populations in Africa have the world’s largest genetic diversity, and SABR will help us understand why people from genetic backgrounds across the world may be more vulnerable to certain diseases, or perhaps respond differently to medication,” says Dr Michèle Ramsay, Director of the Sydney Brenner Institute for Molecular Bioscience (SBIMB) at Wits University.
The SBIMB is integral to a Nature Genetics study that paired whole-genome and blood transcriptome data from over 600 black South African individuals from three different geographic sites to build the SABR.
“Compared to existing resources, SABR gives a clearer picture of gene activity in African populations,” says Dr Stephane Castel of Variant Bio, a SABR collaborator and lead author of the study. “This helps researchers better understand diseases and find genes linked to health conditions in these groups.”
Going beyond African science
While the study focuses on African populations, the SABR can help interpret genetic studies across the world. “It’s about furthering African science while supporting global precision medicine,” says Ramsay.
Until now, the gold standard in functional genomics has been the Genotype-Tissue Expression (GTEx) Project, which is based mainly on individuals of European ancestry. While GTEx is a critical resource, its lack of diversity limits its relevance for other populations, particularly Africans. The SABR helps correct this imbalance. Africans represent the greatest genetic diversity on earth, and SABR now makes it possible to map how genes are switched on or off in blood and how that relates to measurable traits.
A resource with broad relevance
Though focused on blood, the SABR is far from limited to blood-related disorders. Blood is a uniquely accessible tissue that reflects biological processes occurring throughout the body. It carries immune cells, hormones, and metabolic signals, and changes in blood often reflect broader physiological shifts.
What makes the SABR particularly powerful is its ability to detect regulatory variants that have been missed in other datasets. These variants influence how much of a gene is expressed rather than altering the gene sequence itself. In complex diseases—such as cancer, autoimmune conditions, and neurodegenerative disorders—these subtle regulators often play a significant role.
In one striking example, the SABR helped identify a previously unknown gene associated with lipid metabolism that had been missed in European-focused datasets.
“This shows that by including African genomes, we discover things that can benefit everyone,” says Castel.
Despite including a similar number of participants, the SABR identified many more regulatory variants than GTEx. Thanks to Africa’s deep genetic diversity, each individual offers more ‘genetic signals’, making the research more efficient and more informative.
From data to discovery
SABR is already being used to interpret findings from large-scale genetic studies, such as the Pan-UK Biobank, which includes participants of African ancestry. Using co-localisation analysis, researchers can overlay the SABR’s gene regulation data with disease associations from genome-wide association studies (GWAS). This allows them to ask key questions: Which gene is actually driving this disease signal? How is it behaving in the body?
For example, if a GWAS shows a strong genetic association with cancer but the variant lies in a non-coding part of the genome, it may be unclear what gene it affects. The SABR helps bridge this gap by revealing whether the variant increases or decreases gene expression in blood, pointing to the underlying biological mechanism.
“This is the missing link between GWAS and biology,” says Castel. “It helps us understand how a genetic association translates into cellular function and ultimately into disease.”
Built for equity and wider impact
Beyond the science, SABR is also a model for community-engaged and equitable research. Data were collected through partnerships with rural research sites, including the SAMRC/Wits Rural Public Health and Health Transitions Unit (Agincourt) and the Limpopo-situated DIMAMO Population Health Research Centre (University of Limpopo), as well as urban Soweto through the MRC/Wits Developmental Pathways for Health Research Unit. Study researchers travelled across provinces to engage with participants, collect samples, and explain the project’s aims.
The result is a publicly available, African-led dataset designed to accelerate health research globally. Open access means that other scientists can use SABR data to interpret their own studies, including drug development research, which increasingly relies on genomic data to improve trial success rates.
SABR also challenges the idea that bigger is always better. In genomics, diversity can matter more than size. With just a few hundred deeply profiled individuals, SABR has already delivered insights that surpass much larger European datasets.
“Functional genomics has been a missing piece in African genetic research,” says Ramsay. “Now we have it—built in partnership with African scientists, for African health and beyond.”