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

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dc.contributor.authorKintu, Christopher
dc.contributor.authorSoremekun, Opeyemi
dc.contributor.authorMachipisa, Tafadzwa
dc.contributor.authorMayanja, Richard
dc.contributor.authorKalyesubula, Robert
dc.contributor.authorBagaya, Bernard S.
dc.contributor.authorJjingo, Daudi
dc.contributor.authorChikowore, Tinashe
dc.contributor.authorFatumo, Segun
dc.date.accessioned2023-09-14T08:50:48Z
dc.date.available2023-09-14T08:50:48Z
dc.date.issued2023-08-29
dc.date.updated2023-09-03T03:08:37Z
dc.description.abstractDespite 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.
dc.identifier.apacitationKintu, C., Soremekun, O., Machipisa, T., Mayanja, R., Kalyesubula, R., Bagaya, Bernard S., ... Fatumo, S. (2023). Meta-analysis of African ancestry genome-wide association studies identified novel locus and validates multiple loci associated with kidney function. <i>BMC Genomics</i>, 24(1), 496. http://hdl.handle.net/11427/38600en_ZA
dc.identifier.chicagocitationKintu, Christopher, Opeyemi Soremekun, Tafadzwa Machipisa, Richard Mayanja, Robert Kalyesubula, Bernard S. Bagaya, Daudi Jjingo, Tinashe Chikowore, and Segun Fatumo "Meta-analysis of African ancestry genome-wide association studies identified novel locus and validates multiple loci associated with kidney function." <i>BMC Genomics</i> 24, 1. (2023): 496. http://hdl.handle.net/11427/38600en_ZA
dc.identifier.citationKintu, C., Soremekun, O., Machipisa, T., Mayanja, R., Kalyesubula, R., Bagaya, Bernard S., Jjingo, D. & Chikowore, T. et al. 2023. Meta-analysis of African ancestry genome-wide association studies identified novel locus and validates multiple loci associated with kidney function. <i>BMC Genomics.</i> 24(1):496. http://hdl.handle.net/11427/38600en_ZA
dc.identifier.ris TY - Journal Article AU - Kintu, Christopher AU - Soremekun, Opeyemi AU - Machipisa, Tafadzwa AU - Mayanja, Richard AU - Kalyesubula, Robert AU - Bagaya, Bernard S. AU - Jjingo, Daudi AU - Chikowore, Tinashe AU - Fatumo, Segun AB - 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. DA - 2023-08-29 DB - OpenUCT DP - University of Cape Town IS - 1 J1 - BMC Genomics KW - GWAS KW - Africa KW - Kidney function KW - Fine mapping KW - eGFR LK - https://open.uct.ac.za PY - 2023 T1 - Meta-analysis of African ancestry genome-wide association studies identified novel locus and validates multiple loci associated with kidney function TI - Meta-analysis of African ancestry genome-wide association studies identified novel locus and validates multiple loci associated with kidney function UR - http://hdl.handle.net/11427/38600 ER - en_ZA
dc.identifier.urihttps://doi.org/10.1186/s12864-023-09601-0
dc.identifier.urihttp://hdl.handle.net/11427/38600
dc.identifier.vancouvercitationKintu C, Soremekun O, Machipisa T, Mayanja R, Kalyesubula R, Bagaya Bernard S, et al. Meta-analysis of African ancestry genome-wide association studies identified novel locus and validates multiple loci associated with kidney function. BMC Genomics. 2023;24(1):496. http://hdl.handle.net/11427/38600.en_ZA
dc.language.rfc3066en
dc.publisherBioMed Central
dc.publisher.departmentMedicine
dc.publisher.facultyHealth Science
dc.rights.holderBioMed Central Ltd., part of Springer Nature
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.sourceBMC Genomics
dc.source.journalissue1
dc.source.journalvolume24
dc.source.pagination496
dc.source.urihttps://bmcgenomics.biomedcentral.com/
dc.subjectGWAS
dc.subjectAfrica
dc.subjectKidney function
dc.subjectFine mapping
dc.subjecteGFR
dc.titleMeta-analysis of African ancestry genome-wide association studies identified novel locus and validates multiple loci associated with kidney function
dc.typeJournal Article
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