03209nas a2200769 4500008004100000022001400041245008800055210006900143260001300212300001000225490000700235520104200242653002301284653001901307653002201326653003401348653003101382653001101413653001101424653002801435653002701463653001701490653001601507653003601523653001501559653001501574100001901589700002201608700001901630700002001649700001601669700001201685700001601697700002401713700002201737700002201759700002101781700001901802700001901821700002101840700002001861700002001881700002301901700002201924700002001946700002301966700001901989700001702008700002102025700002402046700001702070700002102087700002402108700001902132700002602151700002802177700002302205700002302228700002102251700002002272700002002292700002802312700001802340700002402358700002102382856003602403 2009 eng d a1546-171800aMultiple loci associated with indices of renal function and chronic kidney disease.0 aMultiple loci associated with indices of renal function and chro c2009 Jun a712-70 v413 a
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.
10aChromosome Mapping10aCohort Studies10aGenetic Variation10aGenome-Wide Association Study10aGlomerular Filtration Rate10aHumans10aKidney10aKidney Failure, Chronic10aMeta-Analysis as Topic10aMucoproteins10aNetherlands10aPolymorphism, Single Nucleotide10aPrevalence10aUromodulin1 aKöttgen, Anna1 aGlazer, Nicole, L1 aDehghan, Abbas1 aHwang, Shih-Jen1 aKatz, Ronit1 aLi, Man1 aYang, Qiong1 aGudnason, Vilmundur1 aLauner, Lenore, J1 aHarris, Tamara, B1 aSmith, Albert, V1 aArking, Dan, E1 aAstor, Brad, C1 aBoerwinkle, Eric1 aEhret, Georg, B1 aRuczinski, Ingo1 aScharpf, Robert, B1 aChen, Yii-Der Ida1 ade Boer, Ian, H1 aHaritunians, Talin1 aLumley, Thomas1 aSarnak, Mark1 aSiscovick, David1 aBenjamin, Emelia, J1 aLevy, Daniel1 aUpadhyay, Ashish1 aAulchenko, Yurii, S1 aHofman, Albert1 aRivadeneira, Fernando1 aUitterlinden, André, G1 aDuijn, Cornelia, M1 aChasman, Daniel, I1 aParé, Guillaume1 aRidker, Paul, M1 aKao, Linda, W H1 aWitteman, Jacqueline, C1 aCoresh, Josef1 aShlipak, Michael, G1 aFox, Caroline, S uhttps://chs-nhlbi.org/node/1099