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Association of eGFR-Related Loci Identified by GWAS with Incident CKD and ESRD.
Tuesday,2012-11-06 12:25 America/Los_Angeles — eenright
| Title | Association of eGFR-Related Loci Identified by GWAS with Incident CKD and ESRD. |
| Publication Type | Journal Article |
| Year of Publication | 2011 |
| Authors | Böger, CA, Gorski, M, Li, M, Hoffmann, MM, Huang, C, Yang, Q, Teumer, A, Krane, V, O'Seaghdha, CM, Kutalik, Z, Wichmann, H-E, Haak, T, Boes, E, Coassin, S, Coresh, J, Kollerits, B, Haun, M, Paulweber, B, Köttgen, A, Li, G, Shlipak, MG, Powe, N, Hwang, S-J, Dehghan, A, Rivadeneira, F, Uitterlinden, A, Hofman, A, Beckmann, JS, Krämer, BK, Witteman, J, Bochud, M, Siscovick, D, Rettig, R, Kronenberg, F, Wanner, C, Thadhani, RI, Heid, IM, Fox, CS, Kao, WH |
| Corporate/Institutional Authors | CKDGen Consortium |
| Journal | PLoS Genet |
| Volume | 7 |
| Issue | 9 |
| Pagination | e1002292 |
| Date Published | 2011 Sep |
| ISSN | 1553-7404 |
| Keywords | Adaptor Proteins, Signal Transducing, Adult, Aged, Chronic Disease, Creatinine, European Continental Ancestry Group, Female, Follow-Up Studies, Genetic Association Studies, Humans, Kidney Diseases, Kidney Failure, Chronic, Male, Middle Aged, Polymorphism, Single Nucleotide, Receptor, Epidermal Growth Factor, Uromodulin |
| Abstract | <p>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.</p> |
| DOI | 10.1371/journal.pgen.1002292 |
| Alternate Journal | PLoS Genet. |
| PubMed ID | 21980298 |
| PubMed Central ID | PMC3183079 |
| Grant List | N01HC55020 / HL / NHLBI NIH HHS / United States UL1RR025005 / RR / NCRR NIH HHS / United States N02-HL-6-4278 / HL / NHLBI NIH HHS / United States N01-HC-25195 / HC / NHLBI NIH HHS / United States N01HC55018 / HL / NHLBI NIH HHS / United States R01DK080123 / DK / NIDDK NIH HHS / United States N01-HC-85085 / HC / NHLBI NIH HHS / United States R01HL59367 / HL / NHLBI NIH HHS / United States UL1 RR025005 / RR / NCRR NIH HHS / United States U01 HL080295 / HL / NHLBI NIH HHS / United States N01-HC-55022 / HC / NHLBI NIH HHS / United States N01-HC-85081 / HC / NHLBI NIH HHS / United States R01 HL059367 / HL / NHLBI NIH HHS / United States R01 DK080123 / DK / NIDDK NIH HHS / United States N01 HC015103 / HC / NHLBI NIH HHS / United States N01-HC-55016 / HC / NHLBI NIH HHS / United States R01 HL086694 / HL / NHLBI NIH HHS / United States R01 HL087652 / HL / NHLBI NIH HHS / United States HHSN268200625226C / / PHS HHS / United States U01 HG004402 / HG / NHGRI NIH HHS / United States N01HC55022 / HL / NHLBI NIH HHS / United States R01 DK075787 / DK / NIDDK NIH HHS / United States N01HC55222 / HL / NHLBI NIH HHS / United States N01-HC-55021 / HC / NHLBI NIH HHS / United States N01-HC-85086 / HC / NHLBI NIH HHS / United States N01HC55015 / HL / NHLBI NIH HHS / United States N01HC85086 / HL / NHLBI NIH HHS / United States U01HG004402 / HG / NHGRI NIH HHS / United States N01-HC-85082 / HC / NHLBI NIH HHS / United States 1 R01 DK075787-01A1 / DK / NIDDK NIH HHS / United States P30 DK063491 / DK / NIDDK NIH HHS / United States N01 HC-55222 / HC / NHLBI NIH HHS / United States N01-HC-55019 / HC / NHLBI NIH HHS / United States DK071674 / DK / NIDDK NIH HHS / United States M01RR00425 / RR / NCRR NIH HHS / United States R01 HL062985 / HL / NHLBI NIH HHS / United States R01HL087641 / HL / NHLBI NIH HHS / United States N01-HC-55015 / HC / NHLBI NIH HHS / United States R01 DK084974 / DK / NIDDK NIH HHS / United States R01 DK059616 / DK / NIDDK NIH HHS / United States N01-HC-85083 / HC / NHLBI NIH HHS / United States N01-HC-75150 / HC / NHLBI NIH HHS / United States N01-HC-55020 / HC / NHLBI NIH HHS / United States N01-HC-85080 / HC / NHLBI NIH HHS / United States N01HC55016 / HL / NHLBI NIH HHS / United States R01 AG027002 / AG / NIA NIH HHS / United States 5T32DK007540-25 / DK / NIDDK NIH HHS / United States M01 RR000425 / RR / NCRR NIH HHS / United States N01HC55019 / HL / NHLBI NIH HHS / United States N01HC75150 / HL / NHLBI NIH HHS / United States R01DK059616 / DK / NIDDK NIH HHS / United States N01HC25195 / HL / NHLBI NIH HHS / United States DK063491 / DK / NIDDK NIH HHS / United States R01HL62985 / HL / NHLBI NIH HHS / United States N01-HC-85079 / HC / NHLBI NIH HHS / United States DK084974 / DK / NIDDK NIH HHS / United States R01 HS008365 / HS / AHRQ HHS / United States N01HC85079 / HL / NHLBI NIH HHS / United States N01-HC-55018 / HC / NHLBI NIH HHS / United States N01HC55021 / HL / NHLBI NIH HHS / United States R01 HL087641 / HL / NHLBI NIH HHS / United States N01 HC045133 / HC / NHLBI NIH HHS / United States N01 HC035129 / HC / NHLBI NIH HHS / United States R21 DK071674 / DK / NIDDK NIH HHS / United States N01-HC-85084 / HC / NHLBI NIH HHS / United States T32 DK007540 / DK / NIDDK NIH HHS / United States R01HL086694 / HL / NHLBI NIH HHS / United States R01HS008365 / HS / AHRQ HHS / United States |