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

Please always quote using this URN: urn:nbn:de:bvb:20-opus-133758
  • 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 2,122Family 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.show moreshow less

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Metadaten
Author: Böger Carsten A., 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 Li, Michael 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
URN:urn:nbn:de:bvb:20-opus-133758
Document Type:Journal article
Faculties:Medizinische Fakultät / Medizinische Klinik und Poliklinik I
Language:English
Parent Title (English):PLoS Genetics
Year of Completion:2011
Volume:7
Issue:9
Pagenumber:e1002292
Source:PLoS Genet 7(9): e1002292. doi:10.1371/journal.pgen.1002292
DOI:https://doi.org/10.1371/journal.pgen.1002292
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:African-americans; Chronic Kidney-disease; Diabetic-nephropathy; General-population; Glomerular-filtration-rate; Mortality; Progression; Risk; Stage renal-disease; Variants
Release Date:2019/03/06
Licence (German):License LogoCC 0: Public Domain Dedication