A newly published paper in Nature describes the complex process of launching a nine-country collaboration in Africa to significantly expand scientists’ understanding of human genetic diversity. This can reveal new insights into diseases such as cancer, mental illness, diabetes, and heart disease, benefitting health systems globally.

The Assessing Genetic Diversity in Africa (AGenDA) project has generated whole-genome sequence data from more than 1000 individuals from communities that are largely underrepresented in global genomic databases.

It is anticipated that this effort will uncover millions of novel genetic variants that could reshape how disease risk is predicted and how treatments are tailored.

AGenDA is a deeply collaborative project with balanced contributions developed through a process of co-creation. The study includes hunter-gatherer communities, Nilo-Saharan and Afro-Asiatic speakers, understudied Bantu-speaking groups, and North African and Indian Ocean island communities.

In partnership with local research groups, participants were recruited in Angola, the Democratic Republic of Congo, Kenya, Libya, Mauritius, Rwanda, Tunisia, and Zimbabwe with overall project coordination from South Africa.

“Most genomic datasets that are used to predict disease risk come from people of European origin. As a result, the genetic ‘patterns’ guiding modern medicine are very Eurocentric and poorly predict diseases in African populations. AGenDA was designed to increase representation of African genomic data in global datasets to address this disparity and to ensure that African populations can also benefit,” says Professor Michèle Ramsay, Director of the Sydney Brenner Institute for Molecular Bioscience (SBIMB) at Wits University and lead author of the study.

African genomes are older and more diverse than those of any other continent. Two Africans from different regions can be more genetically different from each other than a European and an Asian. When African data are missing, genetic tools can fail to detect important risk variants and produce inaccurate disease-risk predictions.

“AGenDA is about correcting that imbalance so that genetic research and resulting medical interventions work for African people and for the world,” says Dr Furahini Tluway, AGenDA Project Coordinator at SBIMB and a co-author of the study. “By sequencing whole genomes and not just small genetic panels, we are creating rich reference data that scientists everywhere can use,” she says.

Professor Scott Hazelhurst, SBIMB’s head of bioinformatics, explains the technical impact: “Genome-wide association studies (GWAS) rely on recognising patterns in DNA, but those patterns look very different across populations. Without African data, risk-prediction models are biased and often inaccurate for African patients. By expanding African genome reference data, AGenDA is making GWAS more scientifically robust and more ethically sound.”

Meanwhile AGenDA hopes to be an exemplary research governance model: it is led from the continent by African scientists. Data sharing is managed through African-based data-access committees that review who can use the data, for what purpose and under what conditions. Communities are engaged before any sampling begins, and consent processes are adapted to local languages, cultures, and governance systems.

This approach ensures that participants are not passive subjects of research but informed partners whose rights, values, and expectations shape how data are collected, stored, and shared. It also protects against the historical exploitation of African data without African control.

AGenDA builds on more than a decade of African-led genomic science through the Human Heredity and Health in Africa (H3Africa) Consortium. H3Africa is a pan-African initiative established to strengthen genomics research capacity on the continent and ensure that African populations benefit from genomic medicine. H3Africa has supported dozens of large-scale studies, trained scientists across Africa, and created major genomic resources that are now used globally.

One of these resources is AWI-Gen (Africa Wits-INDEPTH Partnership for Genomic Studies), a flagship H3Africa project co-led from Wits University. AWI-Gen studies the genetic and environmental drivers of cardiometabolic diseases such as diabetes, obesity, and hypertension in African populations.

“The choice of populations for sequencing in genomic studies has usually been chosen from existing samples. Of course, this has resulted in significant gaps in genomic representation in terms of geography and ethnolinguistic diversity. Our strategy of focusing on understudied geographies and identifying partners from these regions has enabled us to address some of the most prominent geographic gaps, such as North Africa, and to make the dataset more comprehensive by including Nilo-Saharan, Afro-Asiatic and African Islander populations that are not adequately represented in current public datasets,” says Dr Ananyo Choudhury, the co-lead for AGenDA and a senior scientist at SBIMB.

In the long term, AGenDA data will help build African genetic reference databases used for disease research, genetic testing, and medicine worldwide. This will improve research on diseases, such as heart disease, diabetes and other chronic illnesses and infections, that strongly affect African populations. In turn, this will make global medical science more accurate.

“Because African genomes contain the deepest branches of human genetic history, they help scientists distinguish genetic variants that are ancient from those that arose more recently and help to detect variants that truly influence disease. Studying African diversity improves genetic science for everyone,” notes Ramsay.