| Title: | Genetic association and transferability for urinary albumin-creatinine ratio as a marker of kidney disease in four Sub-Saharan African populations and non-continental individuals of African ancestry |
| Journal: | Frontiers in Genetics |
| Published: | 15 May 2024 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/38812969/ |
| DOI: | https://doi.org/10.3389/fgene.2024.1372042 |
| URL: | https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2024.1372042/pdf |
Publication 12075
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Abstract
Background: Genome-wide association studies (GWAS) have predominantly focused on populations of European and Asian ancestry, limiting our understanding of genetic factors influencing kidney disease in Sub-Saharan African (SSA) populations. This study presents the largest GWAS for urinary albumin-to-creatinine ratio (UACR) in SSA individuals, including 8,970 participants living in different African regions and an additional 9,705 non-resident individuals of African ancestry from the UK Biobank and African American cohorts.</p>
Methods: Urine biomarkers and genotype data were obtained from two SSA cohorts (AWI-Gen and ARK), and two non-resident African-ancestry studies (UK Biobank and CKD-Gen Consortium). Association testing and meta-analyses were conducted, with subsequent fine-mapping, conditional analyses, and replication studies. Polygenic scores (PGS) were assessed for transferability across populations.</p>
Results: Two genome-wide significant (P < 5 × 10-8) UACR-associated loci were identified, one in the BMP6 region on chromosome 6, in the meta-analysis of resident African individuals, and another in the HBB region on chromosome 11 in the meta-analysis of non-resident SSA individuals, as well as the combined meta-analysis of all studies. Replication of previous significant results confirmed associations in known UACR-associated regions, including THB53, GATM, and ARL15. PGS estimated using previous studies from European ancestry, African ancestry, and multi-ancestry cohorts exhibited limited transferability of PGS across populations, with less than 1% of observed variance explained.</p>
Conclusion: This study contributes novel insights into the genetic architecture of kidney disease in SSA populations, emphasizing the need for conducting genetic research in diverse cohorts. The identified loci provide a foundation for future investigations into the genetic susceptibility to chronic kidney disease in underrepresented African populations Additionally, there is a need to develop integrated scores using multi-omics data and risk factors specific to the African context to improve the accuracy of predicting disease outcomes.</p>
14 Authors
- Jean-Tristan Brandenburg
- Wenlong Carl Chen
- Palwende Romuald Boua
- Melanie A Govender
- Godfred Agongo
- Lisa K Micklesfield
- Hermann Sorgho
- Stephen Tollman
- Gershim Asiki
- Felistas Mashinya
- Scott Hazelhurst
- Andrew P Morris
- June Fabian
- Michèle Ramsay
1 Application
| Application ID | Title |
|---|---|
| 63215 | Comparison and replication of GWAS and gene-environment interaction signals and polygenic risk scores for complex traits in the African AWI-Gen cohort study |
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