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KidneyGenAfrica multi-cohort Genome-wide association study and polygenic prediction of kidney function in 110,000 Africans

Article scientifique 2026 Anglais

Résumé

Kidney disease disproportionately affects populations of African ancestry, yet most genetic studies have focused on Europeans. Here, we present a three-stage genome-wide association study meta-analysis of estimated glomerular filtration rate in ~26,000 individuals across Eastern, Western, and Southern Africa and ~81,000 African-ancestry individuals in the diaspora. Continental African meta-analysis identifies four independent genome-wide significant loci, including two previously unreported loci. Pan-African meta-analysis identifies 19 independent loci, including three previously unreported loci. Fine-mapping reveals four loci with high causality probability, and phenome-wide analyses demonstrate pleiotropic effects on cardiometabolic and immunological traits. Notably, APOL1 high-risk variants strongly associated with kidney disease in African Americans show markedly lower frequency and attenuated effects in continental Africa, indicating potential distinct genetic architectures. Polygenic scores from genetically similar populations significantly outperformed those from distant cohorts. These findings demonstrate the necessity of conducting genomic research across diverse African populations to enable equitable health outcomes.

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Kamiza, A., Chikowore, T., Chen, G., Ojewunmi, O., Machipisa, T., Zhou, F., Mayanja, R., Touré, S., Soremekun, O., Kintu, C., Nakabuye, M., Koprulu, M., Kalungi, A., Kalyesubula, R., Salako, B., Nashiru, O., Corpas, M., Robinson‐Cohen, C., Franceschini, N., Cristian, P., Köttgen, A., Nitsch, D., Langenberg, C., Tcheandjieu, C., Nyirenda, M., Morris, A., Asimit, J., Zeggini, E., Rotimi, C., Ramsay, M., Adeyemo, A., Fabian, J., Crampin, A., Brandenburg, J., Fatumo, S. (2026). KidneyGenAfrica multi-cohort Genome-wide association study and polygenic prediction of kidney function in 110,000 Africans. https://doi.org/10.1038/s41467-026-69367-3

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Auteur(s)

Abram Bunya Kamiza Tinashe Chikowore Guanjie Chen Oyesola Ojewunmi Tafadzwa Machipisa Feng Zhou Richard Mayanja Sounkou M. Touré Opeyemi Soremekun Christopher Kintu Mariam Nakabuye Mine Koprulu Allan Kalungi Robert Kalyesubula Babatunde Salako Oyekanmi Nashiru Manuel Corpas Cassianne Robinson‐Cohen Nora Franceschini Pattaro Cristian Anna Köttgen Dorothea Nitsch Claudia Langenberg Catherine Tcheandjieu Moffat J. Nyirenda Andrew P. Morris Jennifer L. Asimit Eleftheria Zeggini Charles N. Rotimi Michèle Ramsay Adebowale Adeyemo June Fabian Amelia C. Crampin Jean‐Tristan Brandenburg Segun Fatumo

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