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

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 wi...

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Bibliographic Details
Published in:BMC genomics 2023-08, Vol.24 (1), p.496-9, Article 496
Main Authors: Kintu, Christopher, Soremekun, Opeyemi, Machipisa, Tafadzwa, Mayanja, Richard, Kalyesubula, Robert, Bagaya, Bernard S, Jjingo, Daudi, Chikowore, Tinashe, Fatumo, Segun
Format: Article
Language:English
Subjects:
Africa
Black People - genetics
Chromosomes
Chronic kidney failure
Conditional probability
Consortia
Creatinine
Demographic aspects
Disease susceptibility
eGFR
Fine mapping
Gene mapping
Genes
Genetic aspects
Genetics
Genome-wide association studies
Genome-Wide Association Study
Genomes
Genomics
Glomerular filtration rate
GWAS
Hispanic people
Humans
Kidney
Kidney diseases
Kidney function
Kidneys
Meta-analysis
Mitochondrial DNA
Mutation
Pathogenesis
Population
Proteins
Renal function
Renal Insufficiency, Chronic - genetics
Risk factors
Single nucleotide polymorphisms
Single-nucleotide polymorphism
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Summary: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.
ISSN:1471-2164
1471-2164
DOI:10.1186/s12864-023-09601-0