A catalog of genetic loci associated with kidney function from analyses of a million individuals.
Détails
ID Serval
serval:BIB_9B3824B99372
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
A catalog of genetic loci associated with kidney function from analyses of a million individuals.
Périodique
Nature genetics
Collaborateur⸱rice⸱s
Lifelines Cohort Study, V. A. Million Veteran Program
ISSN
1546-1718 (Electronic)
ISSN-L
1061-4036
Statut éditorial
Publié
Date de publication
06/2019
Peer-reviewed
Oui
Volume
51
Numéro
6
Pages
957-972
Langue
anglais
Notes
Publication types: Journal Article ; Meta-Analysis ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Publication Status: ppublish
Résumé
Chronic kidney disease (CKD) is responsible for a public health burden with multi-systemic complications. Through trans-ancestry meta-analysis of genome-wide association studies of estimated glomerular filtration rate (eGFR) and independent replication (n = 1,046,070), we identified 264 associated loci (166 new). Of these, 147 were likely to be relevant for kidney function on the basis of associations with the alternative kidney function marker blood urea nitrogen (n = 416,178). Pathway and enrichment analyses, including mouse models with renal phenotypes, support the kidney as the main target organ. A genetic risk score for lower eGFR was associated with clinically diagnosed CKD in 452,264 independent individuals. Colocalization analyses of associations with eGFR among 783,978 European-ancestry individuals and gene expression across 46 human tissues, including tubulo-interstitial and glomerular kidney compartments, identified 17 genes differentially expressed in kidney. Fine-mapping highlighted missense driver variants in 11 genes and kidney-specific regulatory variants. These results provide a comprehensive priority list of molecular targets for translational research.
Mots-clé
Chromosome Mapping, European Continental Ancestry Group, Genetic Association Studies/methods, Genetic Predisposition to Disease, Genome-Wide Association Study, Glomerular Filtration Rate, Humans, Inheritance Patterns, Kidney Function Tests, Phenotype, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Quantitative Trait, Heritable, Renal Insufficiency, Chronic/genetics, Renal Insufficiency, Chronic/physiopathology, Renal Insufficiency, Chronic/urine, Uromodulin/urine
Pubmed
Web of science
Création de la notice
20/06/2019 6:59
Dernière modification de la notice
20/08/2019 15:02