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Böger, C.A.* ; Gorski, M. ; Li, M.* ; Hoffmann, M.M.* ; Huang, C.* ; Yang, Q.* ; Teumer, A.* ; Krane, V.* ; O'Seaghdha, C.M.* ; Kutalik, Z.* ; Wichmann, H.-E. ; Haak, T.* ; Boes, E.* ; Coassin, S.* ; Coresh, J.* ; Kollerits, B.* ; Haun, M.* ; Paulweber, B.* ; Köttgen, A.* ; Li, G.* ; Shlipak, M.G.* ; Powe, N.* ; Hwang, S.J.* ; Dehghan, A.* ; Rivadeneira, F.* ; Uitterlinden, A.* ; Hofman, A.* ; Beckmann, JS.* ; Krämer, B.K.* ; Witteman, J.* ; Bochud, M.* ; Siscovick, D.* ; Rettig, R.* ; Kronenberg, F.* ; Wanner, C.* ; Thadhani, R.I.* ; Heid, I.M. ; Fox, C.S.* ; Kao, W.H*

Association of eGFR-related loci identified by GWAS with incident CKD and ESRD.

PLoS Genet. 7:e1002292 (2011)
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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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Chronic kidney-disease; Stage renal-disease; Glomerular-filtration-rate; Diabetic-nephropathy; General-population; African-americans; Risk; Progression; Mortality; Variants
Language english
Publication Year 2011
HGF-reported in Year 2011
ISSN (print) / ISBN 1553-7390
e-ISSN 1553-7404
Journal PLoS Genetics
Quellenangaben Volume: 7, Issue: 9, Pages: , Article Number: e1002292 Supplement: ,
Publisher Public Library of Science (PLoS)
Reviewing status Peer reviewed
Institute(s) Institute of Genetic Epidemiology (IGE)
Institute of Epidemiology (EPI)
POF-Topic(s) 30501 - Systemic Analysis of Genetic and Environmental Factors that Impact Health
30503 - Chronic Diseases of the Lung and Allergies
Research field(s) Genetics and Epidemiology
PSP Element(s) G-504100-001
G-503900-001
PubMed ID 21980298
DOI 10.1371/journal.pgen.1002292
Scopus ID 80053457834
Erfassungsdatum 2011-11-23
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