Largest genomic study of kidney function in Africa reveals new genetic risk factors | Newswise

An international research collaboration led by the University of the Witwatersrand and Queen Mary University of London has published the most comprehensive genomic study of kidney function ever conducted in an African population, providing new information on the genetics of chronic kidney disease (CKD) across diverse African populations.

Many newly identified species were common in African populations but completely absent in European and Asian populations, highlighting the importance of performing genomic research directly in African populations rather than from studies conducted elsewhere.

Printed inside Nature Communicationthe study analyzed genomic data from approximately 26,000 people across East, West and South Africa, as well as 81,000 people of African descent living in other countries.

The research was carried out by the KidneyGenAfrica consortium and represents the largest genome-wide association study (GWAS) of kidney function in Africans on the continent to date, expanding the sample size of the previous region by eight times.

The Africa Wits-INDEPTH Partnership for Genomic Studies (AWI-GEN) team, led by Professor Michèle Ramsay, Director of the Sydney Brenner Institute for Molecular Bioscience (SBIMB) at Wits, and the African Research Kidney (ARK) team from Bushbuckridge, Mpumalanga, led by Dr. June Fabian, provided in-depth information.

Fabian is a nephrologist and Director of the Wits Donald Gordon Medical Research Institute. SBIMB researcher, Dr. Jean-Tristan Brandenburg, has ensured that African data is fully represented in these important genomic studies.

Chronic kidney disease affects an estimated 850 million people worldwide, making it the third fastest growing cause of death worldwide. However, its impact is most felt in Africa, where rates of disability and death remain disproportionately high – due to limited access to care for kidney failure, but also a serious research gap.

Despite the disproportionate burden borne by people of African descent, the disease remains largely understudied in these communities. Most genetic studies, including but not limited to kidney disease, have focused on European populations, leaving significant gaps in our understanding of kidney disease risks in Africa.

Using a three-stage GWAS meta-analysis of estimated glomerular filtration rate (eGFR) – an important biomarker of kidney function – the team identified four genes with wide genetic variation in populations of the African continent, including two previously unreported genes. A comprehensive survey of Africa identified 19 key areas, three of which are textbooks.

Ramsay explains: “Our research shows the importance of expanding the diversity of gene expression.

The study also examined polygenic scoring (PGS), tools that combine multiple genes to estimate disease risk. Data derived from genetically similar populations performed significantly better than those based on large but genetically distant populations. This finding highlights the importance of population-based reference data for developing equitable genomic medicine tools.

One of the most interesting findings of the study is about APOLLO1 hereditary. Different types of APOLLO1 are known to triple the risk of kidney disease in African Americans and are strongly associated with the development of kidney failure. Surprisingly, studies show that in the African continent, these high-risk types occur at low levels and have a reduced effect on kidney function compared to the African American diaspora – suggesting that the genetic makeup of kidney disease may differ between African Americans and the population of the African continent. The results warn against using diaspora risk models in populations living in Africa and show that genetic risk for kidney disease varies across African populations, highlighting the scientific value and global health importance of inclusive genomic research. The study team hopes the data will support future work aimed at improving the prevention, diagnosis and treatment of kidney disease worldwide.

Professor Segun Fatumo, Professor and Chair of Genomic Diversity at Queen Mary’s Precision Healthcare University, says, “This research marks a major step in genomic research in Africa. By combining data from across East, West and South Africa, as well as the African diaspora, we have been able to uncover genetic information that would otherwise have been undetectable.

These findings clearly show that when African scientists and global partners work together, we can produce discoveries that not only deepen our understanding of kidney disease but also bring us closer to genomic medicine. KidneyGenAfrica demonstrates the power of collaboration to accelerate science that benefits African communities and the world at large. ”