Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Meta-Analysis
. 2023 Aug 29;24(1):496.
doi: 10.1186/s12864-023-09601-0.

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

Christopher Kintu  1   2 , Opeyemi Soremekun  1   3 , Tafadzwa Machipisa  4 , Richard Mayanja  1   2   3 , Robert Kalyesubula  2   3 , Bernard S Bagaya  2 , Daudi Jjingo  5   6 , Tinashe Chikowore  7   8   9   10 , Segun Fatumo  11   12   13
Affiliations
Meta-Analysis

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

Christopher Kintu et al. BMC Genomics. .

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.

PubMed Disclaimer

Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
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
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
Fig. 3
Quantile–Quantile plot of genome-wide associations of eGFR based on serum creatinine
See this image and copyright information in PMC

References

    1. Eknoyan G, Lameire N, Eckardt K, Kasiske B, Wheeler D, Levin A, Stevens PE, Bilous RW, Lamb EJ, Coresh JJ. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney int. 2013;3(1):5–14.
    1. Eckardt K-U, et al. Evolving importance of kidney disease: from subspecialty to global health burden. Lancet. 2013;382(9887):158–169. doi: 10.1016/S0140-6736(13)60439-0. - DOI - PubMed
    1. Ajayi SO, et al. Prevalence of chronic kidney disease as a marker of hypertension target organ damage in Africa: a systematic review and meta-analysis. Int J Hypertens. 2021;2021:7243523. doi: 10.1155/2021/7243523. - DOI - PMC - PubMed
    1. Xie Y, et al. Analysis of the Global Burden of Disease study highlights the global, regional, and national trends of chronic kidney disease epidemiology from 1990 to 2016. Kidney Int. 2018;94(3):567–581. doi: 10.1016/j.kint.2018.04.011. - DOI - PubMed
    1. Canadas-Garre M, et al. Genetic susceptibility to chronic kidney disease - some more pieces for the heritability puzzle. Front Genet. 2019;10:453. doi: 10.3389/fgene.2019.00453. - DOI - PMC - PubMed

Publication types