New resource illuminates gene activity in African populations<\/p>\n
24 June 2025\u00a0– Wits University<\/p>\n
Newswise \u2014 First-of-its-kind dataset helps us understand why people from genetic backgrounds may be more vulnerable to certain diseases.<\/p>\n
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.<\/p>\n
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.<\/p>\n
With African populations historically underrepresented in genomic research, SABR marks a significant step toward more inclusive and more accurate precision medicine.<\/p>\n
\u201cSABR 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\u2019s 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,\u201d says Dr\u00a0Mich\u00e8le Ramsay<\/a>, Director of the Sydney Brenner Institute for Molecular Bioscience (SBIMB<\/a>) at Wits University.<\/p>\n The SBIMB is integral to a\u00a0Nature Genetics\u00a0study<\/a>\u00a0that paired whole-genome and blood transcriptome data from over 600 black South African individuals from three different geographic sites to build the SABR.<\/p>\n \u201cCompared to existing resources, SABR gives a clearer picture of gene activity in African populations,\u201d says Dr Stephane Castel of\u00a0Variant Bio<\/a>, a SABR collaborator and lead author of the study. \u201cThis helps researchers better understand diseases and find genes linked to health conditions in these groups.\u201d<\/p>\n Going beyond African science<\/p>\n While the study focuses on African populations, the SABR can help interpret genetic studies across the world. \u201cIt\u2019s about furthering African science while supporting global precision medicine,\u201d says Ramsay.<\/p>\n 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.<\/p>\n A resource with broad relevance<\/p>\n 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.<\/p>\n 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\u2014such as cancer, autoimmune conditions, and neurodegenerative disorders\u2014these subtle regulators often play a significant role.<\/p>\n In one striking example, the SABR helped identify a previously unknown gene associated with lipid metabolism that had been missed in European-focused datasets.<\/p>\n \u201cThis shows that by including African genomes, we discover things that can benefit everyone,\u201d says Castel.<\/p>\n Despite including a similar number of participants, the SABR identified many more regulatory variants than GTEx. Thanks to Africa\u2019s deep genetic diversity, each individual offers more \u2018genetic signals\u2019, making the research more efficient and more informative.<\/p>\n From data to discovery<\/p>\n 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\u2019s 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?<\/p>\n 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.<\/p>\n \u201cThis is the missing link between GWAS and biology,\u201d says Castel. \u201cIt helps us understand how a genetic association translates into cellular function and ultimately into disease.\u201d<\/p>\n Built for equity and wider impact<\/p>\n 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<\/a>) 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\u2019s aims.<\/p>\n