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Multiple loci associated with indices of renal function and chronic kidney disease.

Tuesday,2012-11-06 12:18 America/Los_Angeles — eenright
TitleMultiple loci associated with indices of renal function and chronic kidney disease.
Publication TypeJournal Article
Year of Publication2009
AuthorsKöttgen, A, Glazer, NL, Dehghan, A, Hwang, S-J, Katz, R, Li, M, Yang, Q, Gudnason, V, Launer, LJ, Harris, TB, Smith, AV, Arking, DE, Astor, BC, Boerwinkle, E, Ehret, GB, Ruczinski, I, Scharpf, RB, Chen, Y-DI, de Boer, IH, Haritunians, T, Lumley, T, Sarnak, M, Siscovick, D, Benjamin, EJ, Levy, D, Upadhyay, A, Aulchenko, YS, Hofman, A, Rivadeneira, F, Uitterlinden, AG, van Duijn, CM, Chasman, DI, Paré, G, Ridker, PM, Kao, LWH, Witteman, JC, Coresh, J, Shlipak, MG, Fox, CS
JournalNat Genet
Volume41
Issue6
Pagination712-7
Date Published2009 Jun
ISSN1546-1718
KeywordsChromosome Mapping, Cohort Studies, Genetic Variation, Genome-Wide Association Study, Glomerular Filtration Rate, Humans, Kidney, Kidney Failure, Chronic, Meta-Analysis as Topic, Mucoproteins, Netherlands, Polymorphism, Single Nucleotide, Prevalence, Uromodulin
Abstract<p>Chronic kidney disease (CKD) has a heritable component and is an important global public health problem because of its high prevalence and morbidity. We conducted genome-wide association studies (GWAS) to identify susceptibility loci for glomerular filtration rate, estimated by serum creatinine (eGFRcrea) and cystatin C (eGFRcys), and CKD (eGFRcrea < 60 ml/min/1.73 m(2)) in European-ancestry participants of four population-based cohorts (ARIC, CHS, FHS, RS; n = 19,877; 2,388 CKD cases), and tested for replication in 21,466 participants (1,932 CKD cases). We identified significant SNP associations (P < 5 × 10(-8)) with CKD at the UMOD locus, with eGFRcrea at UMOD, SHROOM3 and GATM-SPATA5L1, and with eGFRcys at CST and STC1. UMOD encodes the most common protein in human urine, Tamm-Horsfall protein, and rare mutations in UMOD cause mendelian forms of kidney disease. Our findings provide new insights into CKD pathogenesis and underscore the importance of common genetic variants influencing renal function and disease.</p>
DOI10.1038/ng.377
Alternate JournalNat. Genet.
PubMed ID19430482
PubMed Central IDPMC3039280
Grant ListN01HC55020 / 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
N01 HC055022 / HC / NHLBI NIH HHS / United States
N01 HC085086 / HC / NHLBI NIH HHS / United States
R01 HL059367-02 / HL / NHLBI NIH HHS / United States
P30 DK063491-05 / DK / NIDDK NIH HHS / United States
K01 DK067207 / DK / NIDDK NIH HHS / United States
R01 AG027002-01 / AG / NIA NIH HHS / United States
N01AG12100 / AG / NIA NIH HHS / United States
N01HC55018 / HL / NHLBI 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 HG004402-01 / HG / NHGRI NIH HHS / United States
U01 HL080295 / HL / NHLBI NIH HHS / United States
HL 043851 / HL / NHLBI NIH HHS / United States
N01 HC075150 / HC / NHLBI NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
N01-HC-85081 / HC / NHLBI NIH HHS / United States
R01 HL043851 / HL / NHLBI NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
N01 HC015103 / HC / NHLBI NIH HHS / United States
M01 RR000069 / RR / NCRR NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
N01 HC055018 / HC / NHLBI NIH HHS / United States
N01 HC025195 / HC / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
U01 HL080295-01 / HL / NHLBI NIH HHS / United States
R01 HL087652-01 / 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
N02 HL64278 / HL / WHI NIH HHS / United States
N01HC55222 / HL / NHLBI NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
R01 HL086694-01A1 / HL / 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
CA 047988 / CA / NCI NIH HHS / United States
K01DK067207 / DK / NIDDK NIH HHS / United States
N01-HC-85082 / HC / NHLBI NIH HHS / United States
N01 HC055018 / HC / WHI NIH HHS / United States
N01 HC055019 / HC / NHLBI NIH HHS / United States
P30 DK063491 / DK / NIDDK NIH HHS / United States
/ / Intramural NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
R01HL087641 / HL / NHLBI NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
N01 HC055222 / HC / NHLBI NIH HHS / United States
N01 AG012100 / AG / WHI NIH HHS / United States
N01-HC-55222 / HC / NHLBI NIH HHS / United States
M01RR00069 / RR / NCRR 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 DK076770 / DK / NIDDK NIH HHS / United States
R01 HL043851-09 / HL / NHLBI NIH HHS / United States
N01 HC085079 / HC / WHI NIH HHS / United States
N01 HC055015 / HC / NHLBI NIH HHS / United States
R01 AG027002 / AG / NIA NIH HHS / United States
N01 HC055021 / HC / NHLBI NIH HHS / United States
R01 CA047988 / CA / NCI NIH HHS / United States
N01 HC045133 / HC / WHI NIH HHS / United States
UL1 RR025005-01 / RR / NCRR NIH HHS / United States
N01HC55019 / HL / NHLBI NIH HHS / United States
N01HC75150 / HL / NHLBI NIH HHS / United States
P30 DK063491-019004 / DK / NIDDK NIH HHS / United States
KL2 RR025015 / RR / NCRR NIH HHS / United States
N01HC25195 / HL / NHLBI NIH HHS / United States
R01 HL087641-01 / HL / NHLBI NIH HHS / United States
DK063491 / DK / NIDDK NIH HHS / United States
N01-HC-85079 / HC / NHLBI NIH HHS / United States
N01 HC055020 / HC / NHLBI NIH HHS / United States
UL1 TR000423 / TR / NCATS NIH HHS / United States
N01HC85079 / HL / NHLBI NIH HHS / United States
N01 HC085079 / HC / NHLBI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
N01HC55021 / HL / NHLBI NIH HHS / United States
N01 HC055019 / HC / WHI NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
N01 HC045133 / HC / NHLBI NIH HHS / United States
K01 DK067207-01A1 / DK / NIDDK NIH HHS / United States
N01 HC035129 / HC / NHLBI NIH HHS / United States
N01 HC055016 / HC / NHLBI NIH HHS / United States
N01-HC-85084 / HC / NHLBI NIH HHS / United States
R01HL086694 / HL / NHLBI NIH HHS / United States
KL2 RR025015-03 / RR / NCRR NIH HHS / United States

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