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

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

doi:10.1093/ndt/gfl674

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

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

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

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 language	English
Pages (from-to)	763-771
Number of pages	9
Journal	Nephrology Dialysis Transplantation
Volume	22
Issue number	3
DOIs	https://doi.org/10.1093/ndt/gfl674
State	Published - Mar 2007

Bibliographical note

Funding Information:
Acknowledgements. The HyperGEN network is funded by National Heart, Lung, and Blood Institute R01 HL55673 and cooperative agreements (U10) with National Heart, Lung, and Blood Institute: HL54471 (UT FC), HL54472 (MN Lab), HL54473 (DCC), HL54495 (AL FC), HL54496 (MN FC), HL54509 (NC), HL54515 (UT DNA Lab). The authors are grateful for resources provided by the University of Minnesota Supercomputing Institute.

Funding

Acknowledgements. The HyperGEN network is funded by National Heart, Lung, and Blood Institute R01 HL55673 and cooperative agreements (U10) with National Heart, Lung, and Blood Institute: HL54471 (UT FC), HL54472 (MN Lab), HL54473 (DCC), HL54495 (AL FC), HL54496 (MN FC), HL54509 (NC), HL54515 (UT DNA Lab). The authors are grateful for resources provided by the University of Minnesota Supercomputing Institute.

Funders	Funder number
UT	HL54515, HL54472, HL54473, HL54495, HL54509
National Heart, Lung, and Blood Institute (NHLBI)	U10, U10HL054496, R01 HL55673, HL54471
National Heart, Lung, and Blood Institute (NHLBI)

Keywords

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

ASJC Scopus subject areas

Nephrology
Transplantation

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1093/ndt/gfl674

Cite this

@article{9c3051a949f6478aa7535e6b1b064323,

title = "Genome scan of glomerular filtration rate and albuminuria: The HyperGEN study",

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",

author = "Leon, {Joanlise M.} and Freedman, {Barry I.} and Miller, {Michael B.} and North, {Kari E.} and Hunt, {Steven C.} and Eckfeldt, {John H.} and Lewis, {Cora E.} and Kraja, {Aldi T.} and Luc Djouss{\'e} and Arnett, {Donna K.}",

note = "Funding Information: Acknowledgements. The HyperGEN network is funded by National Heart, Lung, and Blood Institute R01 HL55673 and cooperative agreements (U10) with National Heart, Lung, and Blood Institute: HL54471 (UT FC), HL54472 (MN Lab), HL54473 (DCC), HL54495 (AL FC), HL54496 (MN FC), HL54509 (NC), HL54515 (UT DNA Lab). The authors are grateful for resources provided by the University of Minnesota Supercomputing Institute.",

year = "2007",

month = mar,

doi = "10.1093/ndt/gfl674",

language = "English",

volume = "22",

pages = "763--771",

number = "3",

}

TY - JOUR

T1 - Genome scan of glomerular filtration rate and albuminuria

T2 - The HyperGEN study

AU - Leon, Joanlise M.

AU - Freedman, Barry I.

AU - Miller, Michael B.

AU - North, Kari E.

AU - Hunt, Steven C.

AU - Eckfeldt, John H.

AU - Lewis, Cora E.

AU - Kraja, Aldi T.

AU - Djoussé, Luc

AU - Arnett, Donna K.

N1 - Funding Information: Acknowledgements. The HyperGEN network is funded by National Heart, Lung, and Blood Institute R01 HL55673 and cooperative agreements (U10) with National Heart, Lung, and Blood Institute: HL54471 (UT FC), HL54472 (MN Lab), HL54473 (DCC), HL54495 (AL FC), HL54496 (MN FC), HL54509 (NC), HL54515 (UT DNA Lab). The authors are grateful for resources provided by the University of Minnesota Supercomputing Institute.

PY - 2007/3

Y1 - 2007/3

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.

KW - Albumin to creatinine ratio

KW - Albuminuria

KW - Genome scan

KW - Glomerular filtration rate

KW - Hypertension

KW - Renal function

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JO - Nephrology Dialysis Transplantation

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IS - 3

ER -

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

Abstract

Bibliographical note

Funding

Keywords

ASJC Scopus subject areas

UN SDGs

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