Entebbe, Friday 1^st September 2023 – Chronic kidney disease (CKD) is a growing public health concern across Africa. The main drivers are not well understood, but there has been suspicion genetic factors play a role. Yet its genetic underpinnings remain largely elusive. A groundbreaking study led by scientists at the Medical Research Council/Uganda Virus Research Institute and London School of Hygiene & Tropical Medicine (MRC/UVRI & LSHTM Uganda Research Unit)  sheds important light by identifying new genetic markers of kidney function, with potential to transform our understanding as well as find solutions to this critical health challenge.

Accurately measuring kidney function has been a challenge because the commonly used tool, creatinine-based estimation of glomerular filtration rate (eGFRcrea), performs poorly in sub-Saharan African populations. In this study, titled “Genome-Wide Association Study of Cystatin-C-Based Estimated Glomerular Filtration Rate Reveals Novel Loci in Ugandans,” recently published in eBiomedicine, the authors used cystatin-C to estimate glomerular filtration rate (eGFRcys) which provides a more accurate assessment. The research team then harnessed the power of the Uganda Genomic Resource to conduct an extensive genome-wide association study (GWAS) of  (eGFRcys) in the General Population cohort (GPC) in nearly 6,000 Ugandans.

The study reports two novel genetic variants that had not been previously known to be associated with kidney function in any populations and replicate one variant that has previously been associated with eGFRcys among individuals of European ancestry. The  findings highlight the potential for genomic research to enable new scientific discoveries in sub-Saharan Africa. The potential will be maximally harnessed if rigorous methods (in this case eGFRcys, instead of eGFRcrea) are employed. These discoveries open the door to new research to understand the biological mechanisms, as well as novel prevention and personalized medicine strategies, in Africa and beyond.

Dr Segun Fatumo the lead researcher of the study, emphasized the significance of these findings: “Our work not only expands our understanding of genetic factors influencing kidney function in African populations but also underscores the importance of incorporating advanced biomarkers, such as cystatin-C, to enhance accuracy in assessing kidney health. In addition, our findings highlight the importance of examining genetically diverse population within Africa.” Dr Segun Fatumo leads The Africa Computational Genomics (TACG) Group which is part of the Unit’s NCD Research Theme headed by Prof Moffat Nyirenda. Prof Nyirenda commended Dr Fatumo for this pioneering work and for his leadership in NCD genomics research in Africa, which contributes to the Unit’s mission to conduct high-quality research that adds knowledge and leads to improved control of infectious and non-communicable diseases in Uganda, Africa and globally.

Richard Mayanja, a PhD student at Makerere University who is the first author of the study said: “I am delighted for the opportunity to lead the analysis of this work. Working on this project for my PhD has enhanced my bioinformatics skills and gave me the privilege to collaborate with leading sscientists across the globe.”

In a related study, which was also led by TACG at the Unit and recently published in the Journal BMC Genomics under the title “Meta-analysis of African ancestry genome-wide association studies identified novel locus and validated multiple loci associated with kidney function.” The team identified eight lead genetic variants that are associated with eGFRcrea including one novel genetic variant in about 80,000 African ancestry people.

Christopher Kintu, a PhD student and first author, stated: “Our findings demonstrate the imperative need for larger studies involving people of African ancestry. These efforts have the potential to shed new light on the pathogenesis of chronic kidney disease (CKD) and reveal genomic variants unique to this ancestry that may substantially impact renal health.”

Collectively, these studies not only propel the scientific community toward novel research avenues but also bring genetic insights closer to practical applications. To access the full article and learn more about this paradigm-shifting research, follow the links:

https://www.sciencedirect.com/science/article/pii/S2352396423003419  

https://link.springer.com/article/10.1186/s12864-023-09601-0

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