Meta-analysis of African ancestry genome-wide association studies identified novel locus and validates multiple loci associated with kidney function

Abstract

Despite recent efforts to increase diversity in genome-wide association studies (GWASs), most loci currently associated with kidney function are still limited to European ancestry due to the underlying sample selection bias in available GWASs. We set out to identify susceptibility loci associated with estimated glomerular filtration rate (eGFRcrea) in 80027 individuals of African-ancestry from the UK Biobank (UKBB), Million Veteran Program (MVP), and Chronic Kidney Disease genetics (CKDGen) consortia.We identified 8 lead SNPs, 7 of which were previously associated with eGFR in other populations. We identified one novel variant, rs77408001 which is an intronic variant mapped to the ELN gene. We validated three previously reported loci at GATM-SPATA5L1, SLC15A5 and AGPAT3. Fine-mapping analysis identified variants rs77121243 and rs201602445 as having a 99.9% posterior probability of being causal. Our results warrant designing bigger studies within individuals of African ancestry to gain new insights into the pathogenesis of Chronic Kidney Disease (CKD), and identify genomic variants unique to this ancestry that may influence renal function and disease.

Keywords: Africa; Fine mapping; GWAS; Kidney function; eGFR.

Fig. 1

Manhattan plot for Meta-analysis results showing -log10 (P value) versus genomic position plots for eGFRcrea. Known lead variants are plotted in red, and novel lead variants are in green

Fig. 2

Regional association plot for eGFR in > 80 k African-ancestry individuals from UKBB and MVP consortium at ELN locus. The lead SNP rs77408001 is coloured purple. LD (r2) with other SNPs at the locus was calculated using an African Ancestry reference panel from 1000 Genomes. The arrows represent direction of transcription

Fig. 3

Quantile–Quantile plot of genome-wide associations of eGFR based on serum creatinine