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African ancestry meta-analysis of genome-wide association studies identifies a novel locus and validates multiple loci associated with kidney function

Authors :
Christopher Kintu
Opeyemi Soremekun
Tafadzwa Machipisa
Richard Mayanja
Robert Kalyesubula
Bernard S. Bagaya
Daudi Jjingo
Tinashe Chikowore
Segun Fatumo
Publication Year :
2023
Publisher :
Research Square Platform LLC, 2023.

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 loci, 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 seven previously reported loci at GATM-SPATA5L1 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.

Details

Database :
OpenAIRE
Accession number :
edsair.doi...........ea657ad9e241aad17899b7f293cd1d79
Full Text :
https://doi.org/10.21203/rs.3.rs-2576509/v1