Publication Date
1-10-2024
Journal
Cell Genomics
DOI
10.1016/j.xgen.2023.100468
PMID
38190104
PMCID
PMC10794846
PubMedCentral® Posted Date
12-22-2023
PubMedCentral® Full Text Version
Post-print
Published Open-Access
yes
Keywords
Humans, Genome-Wide Association Study, Renal Insufficiency, Chronic, Glomerular Filtration Rate, Multifactorial Inheritance, Kidney, kidney function, chronic kidney disease, genome-wide association study, multi-ancestry, admixed populations, eGFR, fine-mapping, expression quantitative trait locus, polygenic scores
Abstract
Chronic kidney disease is a leading cause of death and disability globally and impacts individuals of African ancestry (AFR) or with ancestry in the Americas (AMS) who are under-represented in genome-wide association studies (GWASs) of kidney function. To address this bias, we conducted a large meta-analysis of GWASs of estimated glomerular filtration rate (eGFR) in 145,732 AFR and AMS individuals. We identified 41 loci at genome-wide significance (p < 5 × 10−8), of which two have not been previously reported in any ancestry group. We integrated fine-mapped loci with epigenomic and transcriptomic resources to highlight potential effector genes relevant to kidney physiology and disease, and reveal key regulatory elements and pathways involved in renal function and development. We demonstrate the varying but increased predictive power offered by a multi-ancestry polygenic score for eGFR and highlight the importance of population diversity in GWASs and multi-omics resources to enhance opportunities for clinical translation for all.
Graphical Abstract
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Biological Phenomena, Cell Phenomena, and Immunity Commons, Biomedical Informatics Commons, Genetics and Genomics Commons, Medical Genetics Commons, Medical Molecular Biology Commons, Medical Specialties Commons
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