Details

Autor(en) / Beteiligte

• Brandenburg, Jean-Tristan
• Chen, Wenlong Carl
• Boua, Palwende Romuald
• Govender, Melanie A
• Agongo, Godfred
• Micklesfield, Lisa K
• Sorgho, Hermann
• Tollman, Stephen
• Asiki, Gershim
• Mashinya, Felistas
• Hazelhurst, Scott
• Morris, Andrew P
• Fabian, June
• Ramsay, Michèle

Titel

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

Ist Teil von

• Frontiers in genetics, 2024-05, Vol.15, p.1372042-1372042

Ort / Verlag

Switzerland: Frontiers Media S.A

Erscheinungsjahr

2024

Link zum Volltext

Quelle

EZB Electronic Journals Library

Beschreibungen/Notizen

• 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. 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. Two genome-wide significant (P < 5 × 10 ) UACR-associated loci were identified, one in the on chromosome 6 in the meta-analysis of resident African individuals, and another in the 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 , and . 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. 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.