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

Carsten A. Böger, Mathias Gorski, Man Li, Michael M. Hoffmann, Chunmei Huang, Qiong Yang, Alexander Teumer, Vera Krane, Conall M. O'Seaghdha, Zoltán Kutalik, H. Erich Wichmann, Thomas Haak, Eva Boes, Stefan Coassin, Josef Coresh, Barbara Kollerits, Margot Haun, Bernhard Paulweber, Anna Köttgen, Guo LiMichael G. Shlipak, Neil Powe, Shih Jen Hwang, Abbas Dehghan, Fernando Rivadeneira, André Uitterlinden, Albert Hofman, Jacques S. Beckmann, Bernhard K. Krämer, Jacqueline Witteman, Murielle Bochud, David Siscovick, Rainer Rettig, Florian Kronenberg, Christoph Wanner, Ravi I. Thadhani, Iris M. Heid, Caroline S. Fox, W. H. Kao

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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/1.73m2 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.

Original languageEnglish (US)
Article numbere1002292
JournalPLoS genetics
Volume7
Issue number9
DOIs
StatePublished - Sep 2011

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ASJC Scopus subject areas

  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Genetics(clinical)
  • Cancer Research

Cite this

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., ... Kao, W. H. (2011). Association of eGFR-related loci identified by GWAS with incident CKD and ESRD. PLoS genetics, 7(9), [e1002292]. https://doi.org/10.1371/journal.pgen.1002292