Multiple loci associated with indices of renal function and chronic kidney disease.
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.
Köttgen
Anna
A
Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland, USA.
Glazer
Nicole L
NL
Dehghan
Abbas
A
Hwang
Shih-Jen
SJ
Katz
Ronit
R
Li
Man
M
Yang
Qiong
Q
Gudnason
Vilmundur
V
Launer
Lenore J
LJ
Harris
Tamara B
TB
Smith
Albert V
AV
Arking
Dan E
DE
Astor
Brad C
BC
Boerwinkle
Eric
E
Ehret
Georg B
GB
Ruczinski
Ingo
I
Scharpf
Robert B
RB
Chen
Yii-Der Ida
YD
de Boer
Ian H
IH
Haritunians
Talin
T
Lumley
Thomas
T
Sarnak
Mark
M
Siscovick
David
D
Benjamin
Emelia J
EJ
Levy
Daniel
D
Upadhyay
Ashish
A
Aulchenko
Yurii S
YS
Hofman
Albert
A
Rivadeneira
Fernando
F
Uitterlinden
André G
AG
van Duijn
Cornelia M
CM
Chasman
Daniel I
DI
Paré
Guillaume
G
Ridker
Paul M
PM
Kao
W H Linda
WH
Witteman
Jacqueline C
JC
Coresh
Josef
J
Shlipak
Michael G
MG
Fox
Caroline S
CS
D002874:Chromosome Mapping; D015331:Cohort Studies; D014644:Genetic Variation; D055106:Genome-Wide Association Study / Q000379:methods*; D005919:Glomerular Filtration Rate / Q000235:genetics; D006801:Humans; D007668:Kidney / Q000502:physiology* / Q000503:physiopathology; D007676:Kidney Failure, Chronic / Q000453:epidemiology / Q000235:genetics* / Q000503:physiopathology; D015201:Meta-Analysis as Topic; D009088:Mucoproteins / Q000235:genetics*; D009426:Netherlands / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D058949:Uromodulin
D009088:Mucoproteins; C548612:UMOD protein, human; D058949:Uromodulin