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

TL;DR

This study identifies genetic variants linked to kidney function in African populations, highlighting differences in genetic risk factors between African and African-American populations.

Contribution

The study reports novel genetic loci for kidney function in continental Africa and shows distinct genetic architectures compared to African Americans.

Findings

Four independent genome-wide significant loci were identified in continental Africa, including two previously unreported.

Polygenic scores from genetically similar populations outperformed those from distant cohorts in predicting kidney function.

APOL1 high-risk variants showed lower frequency and weaker effects in continental Africa compared to African Americans.

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.

Here, the authors conduct a GWAS for eGFR, then a three-stage regional meta-analysis using GWAS summary data from the Eastern, Western, and Southern African geographical regions. Followed by fine mapping, colocalization, functional annotation, pathway analysis, and phenome-wide association studies showing weaker APOL1 effects in Africa.

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