Journal Article

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

Upadhyay, Ashish, Uitterlinden, André G, Hofman, Albert, Hwang, Shih-Jen, Kao, W H Linda, Ruczinski, Ingo, Siscovick, David, Coresh, Josef, Arking, Dan E, Li, Man, Gudnason, Vilmundur, de Boer, Ian H, Sarnak, Mark, Yang, Qiong, Harris, Tamara B, Boerwinkle, Eric, Dehghan, Abbas, Ridker, Paul M, Ehret, Georg B, Rivadeneira, Fernando, Köttgen, Anna, Chasman, Daniel I, Ida Chen, Yii-Der, van Duijn, Cornelia M, Katz, Ronit, Glazer, Nicole L, Benjamin, Emelia J, Shlipak, Michael G, Smith, Albert V, Launer, Lenore J, Scharpf, Robert B, Witteman, Jacqueline C, Haritunians, Talin, Levy, Daniel, Paré, Guillaume, Aulchenko, Yurii S, Astor, Brad C, Lumley, Thomas, Fox, Caroline S

2009

Overview

Caroline Fox and colleagues report results of a genome-wide association study to identify common variants associated with indices of renal function. They show that variants at UMOD , a gene previously implicated in rare monogenic forms of kidney disease, are associated with risk of chronic kidney disease in the general population. Chronic kidney disease (CKD) has a heritable component and is an important global public health problem because of its high prevalence and morbidity 1 . 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 2 , and rare mutations in UMOD cause mendelian forms of kidney disease 3 . Our findings provide new insights into CKD pathogenesis and underscore the importance of common genetic variants influencing renal function and disease.

• Publisher: Nature Publishing Group US,Nature Publishing Group
• Subject: Agriculture / Animal Genetics and Genomics / Biological and medical sciences / Biomedical and Life Sciences / Biomedicine / Cancer Research / Chromosome Mapping / Chronic illnesses / Cohort Studies / Contracts / Diabetes / Fundamental and applied biological sciences. Psychology / Gene Function / Gene loci / Genetic aspects / Genetic susceptibility / Genetic variance / Genetic Variation / Genetics / Genetics of eukaryotes. Biological and molecular evolution / Genome-Wide Association Study - methods / Glomerular Filtration Rate - genetics / Human Genetics / Humans / Kidney - physiology / Kidney - physiopathology / Kidney diseases / Kidney Failure, Chronic - epidemiology / Kidney Failure, Chronic - genetics / Kidney Failure, Chronic - physiopathology / Kidneys / letter / Medical research / Medical sciences / Meta-Analysis as Topic / Mucoproteins - genetics / Nephrology. Urinary tract diseases / Nephropathies. Renovascular diseases. Renal failure / Netherlands - epidemiology / Physiological aspects / Polymorphism, Single Nucleotide / Prevalence / Public health / Renal failure / Renal function / Risk factors / Statistical methods / Urinary system involvement in other diseases. Miscellaneous / Uromodulin / Validation studies