Multiple Novel Loci are Associated with Indices of Renal Function and Chronic Kidney Disease
By A. Köttgen, N. Glazer, A. Dehghan, Shih-Jen Hwang, R. Katz, Man Li, Qiong Yang, V. Gudnason, Lenore J. Launer, Tamara B. Harris and 29 more. Nature Genetics, 2009
639 citations recorded by the source corpus.
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 m2) 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.
Subfields: Molecular Biology, Nephrology
View Paper: https://www.semanticscholar.org/paper/37971b42d771d3cfd0efcbf81172464f8fd07ec3
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In Molecular Biology
- Silke Szymczak
- Richard J. Johnson
- Markku Laakso
- Andre Franke
- Philippe Froguel
- Carl D. Langefeld
- Sven Bergmann
- James G. Wilson
In Nephrology
Citations in the corpus
- Multiple New Loci Associated with Kidney Function and Chronic Kidney Disease: The CKDGen consortium (2010, neutral): “7) in individuals in the lowest (10) to the highest risk score category (25), and CKD prevalence ranged from 3.”
- A catalog of genetic loci associated with kidney function from analyses of a million individuals (2019, methodology): “The UMOD locus is of particular clinical interest for CKD research:(21) rare UMOD 23 mutations cause autosomal-dominant tubulo-interstitial kidney disease(40), and common 24 variants at UMOD give rise to the strongest eGFR and CKD GWAS signals.(15) We 25 therefore performed conditional analyses base”
- The Rotterdam Study: 2010 objectives and design update (2007, background): “In a large collaborative consortium, the CHARGE consortium, we identified a significant association between chronic kidney disease and the UMOD gene which encodes TammHorsfall protein [42].”
- A genomewide perspective of genetic variation in human metabolism (2009, result): “This is in line with findings of a recent GWAS on kidney function that identified UMOD to be associated with glomerular filtration rat”
- Uric acid and chronic kidney disease: which is chasing which? (2013, background): “Uromodulin polymorphisms have recently been identified by genome-wide screening to be associated with the development of CKD in humans [62].”