Letter abstract
Nature Genetics 41, 712 - 717 (2009)
Published online: 10 May 2009 | doi:10.1038/ng.377
Multiple loci associated with indices of renal function and chronic kidney disease
Anna Köttgen1,25, Nicole L Glazer2,25, Abbas Dehghan3,24,25, Shih-Jen Hwang4,25, Ronit Katz5, Man Li1, Qiong Yang6, Vilmundur Gudnason7,8, Lenore J Launer9, Tamara B Harris9, Albert V Smith7, Dan E Arking10, Brad C Astor1, Eric Boerwinkle11, Georg B Ehret10,12, Ingo Ruczinski13, Robert B Scharpf13, Yii-Der Ida Chen14, Ian H de Boer15, Talin Haritunians14, Thomas Lumley5, Mark Sarnak16, David Siscovick17, Emelia J Benjamin18, Daniel Levy4, Ashish Upadhyay19, Yurii S Aulchenko3, Albert Hofman3, Fernando Rivadeneira20, André G Uitterlinden20, Cornelia M van Duijn3, Daniel I Chasman21, Guillaume Paré21, Paul M Ridker21, W H Linda Kao1, Jacqueline C Witteman3,24,26, Josef Coresh1,13,26, Michael G Shlipak22,26 & Caroline S Fox4,23,26
Chronic kidney disease (CKD) has a heritable component and is an important global public health problem because of its high prevalence and morbidity1. 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 protein2, and rare mutations in UMOD cause mendelian forms of kidney disease3. Our findings provide new insights into CKD pathogenesis and underscore the importance of common genetic variants influencing renal function and disease.
- Department of Epidemiology, Johns Hopkins University, Baltimore, Maryland, USA.
- Cardiovascular Health Research Unit and Department of Medicine, University of Washington, Seattle, Washington, USA.
- Department of Epidemiology, Erasmus Medical Center, Rotterdam, The Netherlands.
- National Heart, Lung, and Blood Institute Framingham Heart Study and the Center for Population Studies, Framingham, Massachusetts, USA.
- Department of Biostatistics, University of Washington, Seattle, Washington, USA.
- Department of Biostatistics, Boston University, Boston, Massachusetts, USA.
- Icelandic Heart Association Research Institute, Kopavogur, Iceland.
- University of Iceland, Reykjavik, Iceland.
- Laboratory of Epidemiology, Demography, and Biometry, Intramural Research Program, National Institute on Aging, Bethesda, Maryland, USA.
- McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins Medical Institutions, Baltimore, Maryland, USA.
- Human Genetics Center and Division of Epidemiology, University of Texas Health Science Center at Houston, Houston, Texas, USA.
- Division of Cardiology, Geneva University Hospital, Switzerland.
- Department of Biostatistics, Johns Hopkins University, Baltimore, Maryland, USA.
- Medical Genetics Institute, Cedars-Sinai Medical Center, Los Angeles, California, USA.
- Division of Nephrology, Department of Medicine, University of Washington, Seattle, Washington, USA.
- Tufts-New England Medical Center, Boston, Massachusetts, USA.
- Departments of Medicine and Epidemiology, Cardiovascular Health Research Unit, University of Washington, Seattle, Washington, USA.
- Boston University Schools of Medicine and Public Health, Boston, Massachusetts, USA.
- Renal Section, Boston Medical Center and Boston University School of Medicine, Boston, Massachusetts, USA.
- Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
- Division of Preventive Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA.
- General Internal Medicine Division, San Francisco VA Medical Center, University of California, San Francisco, California, USA.
- Brigham and Women's Hospital Division of Endocrinology and Harvard Medical School, Boston, Massachusetts, USA.
- Member of the Netherlands Consortium on Healthy Aging (NCHA).
- These authors contributed equally to this work.
- These authors jointly directed the project.
Correspondence to: Caroline S Fox4,23,26 e-mail: foxca@nhlbi.nih.gov
Correspondence to: Jacqueline C Witteman3,24,26 e-mail: j.witteman@erasmusmc.nl
Correspondence to: Josef Coresh1,13,26 e-mail: coresh@jhu.edu
Correspondence to: Michael G Shlipak22,26 e-mail: michael.shlipak@ucsf.edu
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