RGD Reference Report - Association of eGFR-Related Loci Identified by GWAS with Incident CKD and ESRD. - Rat Genome Database

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Association of eGFR-Related Loci Identified by GWAS with Incident CKD and ESRD.

Authors: Boger, CA  Gorski, M  Li, M  Hoffmann, MM  Huang, C  Yang, Q  Teumer, A  Krane, V  O'Seaghdha, CM  Kutalik, Z  Wichmann, HE  Haak, T  Boes, E  Coassin, S  Coresh, J  Kollerits, B  Haun, M  Paulweber, B  Kottgen, A  Li, G  Shlipak, MG  Powe, N  Hwang, SJ  Dehghan, A  Rivadeneira, F  Uitterlinden, A  Hofman, A  Beckmann, JS  Kramer, BK  Witteman, J  Bochud, M  Siscovick, D  Rettig, R  Kronenberg, F  Wanner, C  Thadhani, RI  Heid, IM  Fox, CS  Kao, WH  Kao, WH 
Citation: Boger CA, etal., PLoS Genet. 2011 Sep;7(9):e1002292. doi: 10.1371/journal.pgen.1002292. Epub 2011 Sep 29.
RGD ID: 7242279
Pubmed: PMID:21980298   (View Abstract at PubMed)
PMCID: PMC3183079   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pgen.1002292   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GCKRHumanend stage renal disease  IMP DNA: snp: rs1260326RGD 
GckrRatend stage renal disease  ISOGCKR (Homo sapiens)DNA: snp: rs1260326RGD 
GckrMouseend stage renal disease  ISOGCKR (Homo sapiens)DNA: snp: rs1260326RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gckr  (glucokinase regulator)

Genes (Mus musculus)
Gckr  (glucokinase regulatory protein)

Genes (Homo sapiens)
GCKR  (glucokinase regulator)


Additional Information