Genome-wide association study of kidney function decline in individuals of European descent.
Détails
Télécharger: BIB_536FB4F7B8E1.P001.pdf (1242.58 [Ko])
Etat: Public
Version: de l'auteur⸱e
Etat: Public
Version: de l'auteur⸱e
ID Serval
serval:BIB_536FB4F7B8E1
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Genome-wide association study of kidney function decline in individuals of European descent.
Périodique
Kidney International
ISSN
1523-1755 (Electronic)
ISSN-L
0085-2538
Statut éditorial
Publié
Date de publication
05/2015
Peer-reviewed
Oui
Volume
87
Numéro
5
Pages
1017-1029
Langue
anglais
Notes
IUMSP2015/05
Résumé
Genome-wide association studies (GWASs) have identified multiple loci associated with cross-sectional eGFR, but a systematic genetic analysis of kidney function decline over time is missing. Here we conducted a GWAS meta-analysis among 63,558 participants of European descent, initially from 16 cohorts with serial kidney function measurements within the CKDGen Consortium, followed by independent replication among additional participants from 13 cohorts. In stage 1 GWAS meta-analysis, single-nucleotide polymorphisms (SNPs) at MEOX2, GALNT11, IL1RAP, NPPA, HPCAL1, and CDH23 showed the strongest associations for at least one trait, in addition to the known UMOD locus, which showed genome-wide significance with an annual change in eGFR. In stage 2 meta-analysis, the significant association at UMOD was replicated. Associations at GALNT11 with Rapid Decline (annual eGFR decline of 3 ml/min per 1.73 m(2) or more), and CDH23 with eGFR change among those with CKD showed significant suggestive evidence of replication. Combined stage 1 and 2 meta-analyses showed significance for UMOD, GALNT11, and CDH23. Morpholino knockdowns of galnt11 and cdh23 in zebrafish embryos each had signs of severe edema 72 h after gentamicin treatment compared with controls, but no gross morphological renal abnormalities before gentamicin administration. Thus, our results suggest a role in the deterioration of kidney function for the loci GALNT11 and CDH23, and show that the UMOD locus is significantly associated with kidney function decline.Kidney International advance online publication, 10 December 2014; doi:10.1038/ki.2014.361.
Pubmed
Web of science
Création de la notice
15/12/2014 13:11
Dernière modification de la notice
20/08/2019 14:08