Association of eGFR-Related Loci Identified by GWAS with Incident CKD and ESRD.
Details
Download: BIB_CB7DEB898419.P001.pdf (125.03 [Ko])
State: Public
Version: Final published version
State: Public
Version: Final published version
Serval ID
serval:BIB_CB7DEB898419
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Association of eGFR-Related Loci Identified by GWAS with Incident CKD and ESRD.
Journal
Plos Genetics
Working group(s)
CKDGen Consortium
ISSN
1553-7404 (Electronic)
ISSN-L
1553-7390
Publication state
Published
Issued date
2011
Peer-reviewed
Oui
Volume
7
Number
9
Pages
e1002292
Language
english
Abstract
Family studies suggest a genetic component to the etiology of chronic kidney disease (CKD) and end stage renal disease (ESRD). Previously, we identified 16 loci for eGFR in genome-wide association studies, but the associations of these single nucleotide polymorphisms (SNPs) for incident CKD or ESRD are unknown. We thus investigated the association of these loci with incident CKD in 26,308 individuals of European ancestry free of CKD at baseline drawn from eight population-based cohorts followed for a median of 7.2 years (including 2,122 incident CKD cases defined as eGFR <60ml/min/1.73m(2) at follow-up) and with ESRD in four case-control studies in subjects of European ancestry (3,775 cases, 4,577 controls). SNPs at 11 of the 16 loci (UMOD, PRKAG2, ANXA9, DAB2, SHROOM3, DACH1, STC1, SLC34A1, ALMS1/NAT8, UBE2Q2, and GCKR) were associated with incident CKD; p-values ranged from p = 4.1e-9 in UMOD to p = 0.03 in GCKR. After adjusting for baseline eGFR, six of these loci remained significantly associated with incident CKD (UMOD, PRKAG2, ANXA9, DAB2, DACH1, and STC1). SNPs in UMOD (OR = 0.92, p = 0.04) and GCKR (OR = 0.93, p = 0.03) were nominally associated with ESRD. In summary, the majority of eGFR-related loci are either associated or show a strong trend towards association with incident CKD, but have modest associations with ESRD in individuals of European descent. Additional work is required to characterize the association of genetic determinants of CKD and ESRD at different stages of disease progression.
Keywords
Adaptor Proteins, Signal Transducing/genetics, Adult, Aged, Chronic Disease, Creatinine/blood, European Continental Ancestry Group/genetics, Female, Follow-Up Studies, Genetic Association Studies, Humans, Kidney Diseases/etiology, Kidney Diseases/genetics, Kidney Failure, Chronic/etiology, Kidney Failure, Chronic/genetics, Male, Middle Aged, Polymorphism, Single Nucleotide, Receptor, Epidermal Growth Factor/genetics, Uromodulin/genetics
Pubmed
Web of science
Open Access
Yes
Create date
13/10/2011 15:55
Last modification date
20/08/2019 15:46