KidneyGenAfrica multi-cohort Genome-wide association study and polygenic prediction of kidney function in 110,000 Africans
Abstract
Abstract 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.
Article Details
Authors (35)
Abram B. Kamiza
Tinashe Chikowore
Guanjie Chen
Oyesola Ojewunmi
Tafadzwa Machipisa
Feng Zhou
Richard Mayanja
Sounkou Toure
Opeyemi Soremekun
Christopher Kintu
Mariam Nakabuye
Mine Koprulu
Allan Kalungi
Robert Kalyesubula
Babatunde Salako
Oyekanmi Nashiru
Manuel Corpas
Cassianne Robinson-Cohen
Nora Franceschini
University of North Carolina, Chapel Hill, NC, USA.
Cristian Pattaro
Anna Köttgen
Dorothea Nitsch
Claudia Langenberg
Catherine Tcheandjieu
Moffat Nyirenda
Andrew P. Morris
Jennifer Asimit
Eleftheria Zeggini
Charles Rotimi
Michèle Ramsay
Adebowale Adeyemo
June Fabian
Amelia C. Crampin
Jean-Tristan Brandenburg
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