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NDT Advance Access originally published online on December 21, 2006
Nephrology Dialysis Transplantation 2007 22(3):763-771; doi:10.1093/ndt/gfl674
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© The Author [2006]. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Genome scan of glomerular filtration rate and albuminuria: the HyperGEN study

Joanlise M. Leon1, Barry I. Freedman2, Michael B. Miller1, Kari E. North3, Steven C. Hunt4, John H. Eckfeldt5, Cora E. Lewis6, Aldi T. Kraja7, Luc Djoussé8 and Donna K. Arnett9

1Division of Epidemiology and Community Health, University of Minnesota, Minneapolis, MN, 2Department of Internal Medicine/Nephrology, Wake Forest University, Winston-Salem and 3Department of Epidemiology, University of North Carolina at Chapel Hill, Chapel Hill, NC, 4Cardiovascular Genetics Division, Department of Internal Medicine, University of Utah, Salt Lake City, UT, 5Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN, 6Division of Preventive Medicine, University of Alabama at Birmingham, Birmingham, AL, 7Division of Statistical Genomics, Washington University School of Medicine, St Louis, MO, 8Section of Preventive Medicine & Epidemiology, Department of Medicine, Boston University School of Medicine, Boston, MD and 9Department of Epidemiology, University of Alabama at Birmingham, Birmingham, AL, USA

Correspondence and offprint requests to: Joanlise Leon, Division of Epidemiology – School of Public Health, University of Minnesota, Minneapolis, USA. Email: leon{at}epi.umn.edu



  Abstract

Background. Albuminuria and reduced glomerular filtration rate (GFR) are markers of renal dysfunction associated with hypertension. We performed genome-wide scans to detect loci impacting these parameters in 1251 African American (AAs) and 1129 European American (EAs) hypertensive siblings from the Hypertension Genetic Epidemiology Network study.

Methods. GFR, estimated by the Modification of Diet in Renal Disease equation, and albuminuria, measured as albumin to creatinine ratio (ACR), were adjusted for gender, age, centre, mean blood pressure, anti-hypertensive medication class and diabetes status using SOLAR. Since albuminuria and abnormal GFR often coexist, we conducted bivariate linkage analyses to investigate the presence of pleiotropy.

Results. The phenotypic correlation between ACR and GFR was not significant in EAs (r = 0.04) and significantly negative in AAs (r = –0.17). Univariate analyses of ACR showed suggestive evidence of linkage on chromosomes 8, 16 and 17 (LOD: 2–2.8) in AAs, on chromosomes 18 and 19 (LOD = 2) in EAs, and on chromosome 19 (LOD = 2.6) when combining AAs and EAs. For GFR, suggestive linkage was found on chromosomes 7, 14 and 19 (LOD: 2.2–2.9) in AAs and on chromosomes 14, 15 and 16 (LOD: 2.1–3.3) in the combined group. Also, bivariate analyses showed a LOD score of 3.4 at 133 cM on chromosome 7 in AAs.

Conclusions. Suggestive evidence for linkage to GFR and ACR was observed at many loci. The findings are consistent with previous studies. Also, indication of a pleiotropic locus was detected in chromosome 7 in AAs.

Keywords: albumin to creatinine ratio; albuminuria; genome scan; glomerular filtration rate; hypertension; renal function

Received for publication: 27. 1.06
Accepted in revised form: 19.10.06


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Lumping, splitting and mapping: assessing linkage in different ethnic groups for albuminuria and glomerular filtration rate in the HyperGen study
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