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

Joanlise M. Leon, Barry I. Freedman, Michael B. Miller, Kari E. North, Steven Hunt, John H. Eckfeldt, Cora E. Lewis, Aldi T. Kraja, Luc Djoussé, Donna K. Arnett

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)763-771
Number of pages9
JournalNephrology Dialysis Transplantation
Volume22
Issue number3
DOIs
Publication statusPublished - Mar 2007
Externally publishedYes

Fingerprint

Albuminuria
Glomerular Filtration Rate
African Americans
Genome
Chromosomes, Human, Pair 19
Chromosomes, Human, Pair 7
Albumins
Creatinine
Chromosomes, Human, Pair 16
Chromosomes, Human, Pair 14
Hypertension
Diet Therapy
Kidney
Chromosomes, Human, Pair 18
Chromosomes, Human, Pair 15
Chromosomes, Human, Pair 8
Chromosomes, Human, Pair 17
Molecular Epidemiology
Antihypertensive Agents
Siblings

Keywords

  • Albumin to creatinine ratio
  • Albuminuria
  • Genome scan
  • Glomerular filtration rate
  • Hypertension
  • Renal function

ASJC Scopus subject areas

  • Nephrology
  • Transplantation

Cite this

Leon, J. M., Freedman, B. I., Miller, M. B., North, K. E., Hunt, S., Eckfeldt, J. H., ... Arnett, D. K. (2007). Genome scan of glomerular filtration rate and albuminuria: The HyperGEN study. Nephrology Dialysis Transplantation, 22(3), 763-771. https://doi.org/10.1093/ndt/gfl674

Genome scan of glomerular filtration rate and albuminuria : The HyperGEN study. / Leon, Joanlise M.; Freedman, Barry I.; Miller, Michael B.; North, Kari E.; Hunt, Steven; Eckfeldt, John H.; Lewis, Cora E.; Kraja, Aldi T.; Djoussé, Luc; Arnett, Donna K.

In: Nephrology Dialysis Transplantation, Vol. 22, No. 3, 03.2007, p. 763-771.

Research output: Contribution to journalArticle

Leon, JM, Freedman, BI, Miller, MB, North, KE, Hunt, S, Eckfeldt, JH, Lewis, CE, Kraja, AT, Djoussé, L & Arnett, DK 2007, 'Genome scan of glomerular filtration rate and albuminuria: The HyperGEN study', Nephrology Dialysis Transplantation, vol. 22, no. 3, pp. 763-771. https://doi.org/10.1093/ndt/gfl674
Leon, Joanlise M. ; Freedman, Barry I. ; Miller, Michael B. ; North, Kari E. ; Hunt, Steven ; Eckfeldt, John H. ; Lewis, Cora E. ; Kraja, Aldi T. ; Djoussé, Luc ; Arnett, Donna K. / Genome scan of glomerular filtration rate and albuminuria : The HyperGEN study. In: Nephrology Dialysis Transplantation. 2007 ; Vol. 22, No. 3. pp. 763-771.
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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.",
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AU - North, Kari E.

AU - Hunt, Steven

AU - Eckfeldt, John H.

AU - Lewis, Cora E.

AU - Kraja, Aldi T.

AU - Djoussé, Luc

AU - Arnett, Donna K.

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N2 - 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.

AB - 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.

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KW - Renal function

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