It is estimated more than 500,000 individuals succumb to end stage renal disease annually in sub-Saharan Africa with an additional 50 million people suffering from pre-dialysis chronic kidney disease. Advanced genome-based analysis strategies, such as Mapping by Admixture Linkage Disequilibrium (MALD) in African Americans, have identified a strong association between single gene variants (e.g., MYH9 and AP0L1) and kidney disease. In addition, nearly 20 genetic variants have been linked to childhood onset nephrotic syndrome. Most of these genetic advances in elucidating the etiology of kidney disease have occurred outside sub-Saharan Africa where there is a shortage of genetic experts and the infrastructure for human genomic research is as sparse as the Sahara Desert itself. In this application, we propose to rapidly increase the capacity to conduct genomic studies of kidney disease in sub-Saharan Africa through a collaborative research network comprised of investigators based at 10 institutions in five African countries - pop. 362 million (Ethiopia, Ghana, Kenya, Nigeria and South Africa) and four North American institutions. The Network will accomplish the following seven objectives: (1) phenotype 8,000 kidney disease cases and controls (1:1);(2) conduct four genetic research projects addressing single gene mutation kidney disorders in affected families, genetic variants of single genes associated with kidney diseases in the populations and genome wide association studies;(3) establish two low-capital intensity, rugged and sustainable genomics research laboratories in Africa;(4) implement a customized six-track training and career development plan for African-based genomic researchers;(5) establish and maintain a Network-wide biospecimen repository that will harmonize seamlessly with the H3Africa Biorepository Grants (RFA-RM-11-011);(6) establish and maintain a Network-wide data management and bioinformatics facility that will effectively integrate with the H3Africa Bioinformatics Network (RFA-RM-11-010) and (7) cooperate and coordinate the activities of this Network with the H3Africa Consortium and the NIH Program Scientists/Staff. This application is submitted by the University of Ghana with substantial institutional support from the University of Michigan.

Public Health Relevance

More than 500,000 people die from kidney failure annually in sub-Saharan Africa. Recent advances in genomic science suggest a strong genetic component to the excess risk of kidney failure in African Americans who have 3- to 4-fold greater risk of kidney disease compared to Whites. The projects in this application will enable African-based scientists to conduct genetic research to elucidate the hereditary and environmental factors that predisposes people in sub-Saharan Africa to a high risk of kidney failure.

National Institute of Health (NIH)
National Human Genome Research Institute (NHGRI)
Specialized Center--Cooperative Agreements (U54)
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Struewing, Jeffery P
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Noguchi Memorial Institute / Medical Research
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