Largest genomic study of kidney function in Africa reveals new genetic risk factors
- 91心頭利 University
Widening diversity in genomic datasets opens the door to discovering variants and biological pathways and thereby strengthening genomic science for everyone.
An international research collaboration led by the 91心頭利 and Queen Mary University of London has published the most comprehensive genomic investigation of kidney function ever conducted in African populations, shedding new light on the genetics of chronic kidney disease (CKD) across diverse African populations.
Several newly identified variants were common in African populations but entirely absent in European and Asian populations, highlighting the importance of conducting genomic research directly within African populations rather than extrapolating from studies conducted elsewhere.
in Nature Communications, the study analysed genomic data from approximately 26,000 individuals across Eastern, Western, and South Africa, alongside 81,000 individuals of African ancestry in the diaspora.
The research was conducted through the consortium and represents the largest genome-wide association study (GWAS) of kidney function in continental Africans to date, expanding previous regional sample sizes by eightfold.
The Africa 91心頭利-INDEPTH Partnership for Genomic Studies () cohort, led by Professor Michèle Ramsay, Director of the Sydney Brenner Institute for Molecular Bioscience () at 91心頭利, and the African Research Kidney (ARK) cohort from Bushbuckridge, Mpumalanga, led by Dr June Fabian, provided the critical data for the publication.
Fabian is a nephrologist and the Director of the Medical Research Institute. SBIMB researcher, Dr , ensured that African data was thoroughly represented in this landmark genomic investigation.
Chronic kidney disease affects an estimated 850 million people worldwide, making it the third fastest-growing cause of death globally. Yet its impact is felt most acutely in Africa, where rates of disability and death remain disproportionately high — a consequence of limited access to care for kidney failure, but also a deeper research gap.
Despite the disproportionate burden carried by people of African ancestry, the disease remains critically understudied in these communities. Most genetic research, including but not limited to kidney disease, has focused on European populations, leaving significant gaps in our understanding of the biological drivers of kidney disease risk in Africa.
Using a three-stage GWAS meta-analysis of estimated glomerular filtration rate (eGFR) – a key biomarker of kidney function – the team identified four genome-wide significant genetic loci in continental African populations, including two previously unreported variants. A broader pan-African analysis identified 19 significant loci, three of which are novel.
Ramsay explains: “Our study demonstrates the importance of widening diversity in genomic datasets. While historic datasets have been invaluable for genomic research, adding more data from the same populations is now yielding fewer new insights. Studying the rich genetic diversity found in African populations opens the door to discovering variants and biological pathways that may not be visible elsewhere, strengthening genomic science for everyone.”
The study also examined polygenic scores (PGS), tools that combine many genetic variants to estimate disease risk. Scores derived from genetically similar populations performed significantly better than those based on larger but more genetically distant datasets. This finding highlights the importance of population-matched reference data for developing equitable genomic medicine tools.
One of the study's most striking findings concerns the APOL1 gene. Variants in APOL1 are known to increase kidney disease risk threefold in African Americans and are strongly associated with progression to kidney failure. Surprisingly, the findings show that in continental Africa, these high-risk variants occur at lower frequencies and with reduced effects on kidney function when compared to the African American diaspora – suggesting that the genetic architecture of kidney disease may differ between African Americans and continental African populations. The results caution against applying diaspora-derived risk models to populations living in Africa and demonstrates that genetic risk for kidney disease varies across African populations, highlighting both the scientific value and the global health importance of inclusive genomic research. The study team hopes that the dataset will support future work aimed at improving prevention, diagnosis and treatment of kidney disease worldwide.
Professor Segun Fatumo, Professor and Chair of Genomic Diversity at Queen Mary’s Precision Healthcare University Research Institute, says, “This study marks a major milestone for genomic research in Africa. By combining data from across Eastern, Western and Southern Africa, as well as the African diaspora, we have been able to uncover genetic insights that would have been impossible to detect otherwise.
These findings show clearly that when African scientists and global partners work collaboratively, we can generate discoveries that not only deepen our understanding of kidney disease but also move us closer to equitable genomic medicine. KidneyGenAfrica demonstrates the power of partnerships to accelerate science that benefits communities in Africa and around the world.”