The African Computational Genomics (TACG) Research Group, MRC/UVRI and LSHTM Uganda Research Unit, Entebbe, Uganda.
Department of Immunology and Molecular Biology, School of Biomedical Sciences, Makerere University College of Health Sciences, Kampala, Uganda.
BMC Genomics. 2023 Aug 29;24(1):496. doi: 10.1186/s12864-023-09601-0.
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.
尽管最近努力增加全基因组关联研究（GWAS）中的多样性，但由于现有 GWAS 中存在潜在的样本选择偏差，目前与肾功能相关的大多数基因座仍然仅限于欧洲血统。我们着手确定与英国生物银行（UKBB）、百万退伍军人计划（MVP）和慢性肾脏病遗传学（CKDGen）联盟中 80027 名非洲裔个体的估计肾小球滤过率（eGFRcrea）相关的易感基因座。我们确定了 8 个主要的 SNP，其中 7 个在其他人群中与 eGFR 相关。我们确定了一个新的变体 rs77408001，它是一个映射到 ELN 基因的内含子变体。我们验证了三个先前报道的位于 GATM-SPATA5L1、SLC15A5 和 AGPAT3 上的位点。精细映射分析确定变体 rs77121243 和 rs201602445 具有 99.9%的因果后验概率。我们的结果证明有必要在非洲裔个体中进行更大规模的研究，以深入了解慢性肾脏病（CKD）的发病机制，并确定该血统特有的影响肾功能和疾病的基因组变异。
