Genome scan of glomerular filtration rate and albuminuria: the HyperGEN study.
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.
Leon
Joanlise M
JM
Division of Epidemiology, School of Public Health, University of Minnesota, Minneapolis, USA. leon@epi.umn.edu
Freedman
Barry I
BI
Miller
Michael B
MB
North
Kari E
KE
Hunt
Steven C
SC
Eckfeldt
John H
JH
Lewis
Cora E
CE
Kraja
Aldi T
AT
Djoussé
Luc
L
Arnett
Donna K
DK
D000418:Albumins / Q000378:metabolism; D000419:Albuminuria / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D003404:Creatinine / Q000378:metabolism; D003430:Cross-Sectional Studies; D018450:Disease Progression; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D015894:Genome, Human; D005838:Genotype; D005919:Glomerular Filtration Rate / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype
D000418:Albumins; D003404:Creatinine