Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2013 Dec 17;8(12):e81888.
doi: 10.1371/journal.pone.0081888. eCollection 2013.

A genome-wide search for linkage of estimated glomerular filtration rate (eGFR) in the Family Investigation of Nephropathy and Diabetes (FIND)

Farook Thameem  1 , Robert P Igo Jr  2 , Barry I Freedman  3 , Carl Langefeld  3 , Robert L Hanson  4 , Jeffrey R Schelling  5 , Robert C Elston  2 , Ravindranath Duggirala  6 , Susanne B Nicholas  7 , Katrina A B Goddard  8 , Jasmin Divers  3 , Xiuqing Guo  9 , Eli Ipp  10 , Paul L Kimmel  11 , Lucy A Meoni  12 , Vallabh O Shah  13 , Michael W Smith  14 , Cheryl A Winkler  15 , Philip G Zager  13 , William C Knowler  4 , Robert G Nelson  4 , Madeline V Pahl  16 , Rulan S Parekh  17 , W H Linda Kao  12 , Rebekah S Rasooly  11 , Sharon G Adler  10 , Hanna E Abboud  1 , Sudha K Iyengar  2 , John R Sedor  2 ; Family Investigation of Nephropathy and Diabetes Research Group
Affiliations

A genome-wide search for linkage of estimated glomerular filtration rate (eGFR) in the Family Investigation of Nephropathy and Diabetes (FIND)

Farook Thameem et al. PLoS One. .

Abstract

Objective: Estimated glomerular filtration rate (eGFR), a measure of kidney function, is heritable, suggesting that genes influence renal function. Genes that influence eGFR have been identified through genome-wide association studies. However, family-based linkage approaches may identify loci that explain a larger proportion of the heritability. This study used genome-wide linkage and association scans to identify quantitative trait loci (QTL) that influence eGFR.

Methods: Genome-wide linkage and sparse association scans of eGFR were performed in families ascertained by probands with advanced diabetic nephropathy (DN) from the multi-ethnic Family Investigation of Nephropathy and Diabetes (FIND) study. This study included 954 African Americans (AA), 781 American Indians (AI), 614 European Americans (EA) and 1,611 Mexican Americans (MA). A total of 3,960 FIND participants were genotyped for 6,000 single nucleotide polymorphisms (SNPs) using the Illumina Linkage IVb panel. GFR was estimated by the Modification of Diet in Renal Disease (MDRD) formula.

Results: The non-parametric linkage analysis, accounting for the effects of diabetes duration and BMI, identified the strongest evidence for linkage of eGFR on chromosome 20q11 (log of the odds [LOD] = 3.34; P = 4.4 × 10(-5)) in MA and chromosome 15q12 (LOD = 2.84; P = 1.5 × 10(-4)) in EA. In all subjects, the strongest linkage signal for eGFR was detected on chromosome 10p12 (P = 5.5 × 10(-4)) at 44 cM near marker rs1339048. A subsequent association scan in both ancestry-specific groups and the entire population identified several SNPs significantly associated with eGFR across the genome.

Conclusion: The present study describes the localization of QTL influencing eGFR on 20q11 in MA, 15q21 in EA and 10p12 in the combined ethnic groups participating in the FIND study. Identification of causal genes/variants influencing eGFR, within these linkage and association loci, will open new avenues for functional analyses and development of novel diagnostic markers for DN.

PubMed Disclaimer

Conflict of interest statement

Competing Interests: The first author Farook Thameem is a PLOS ONE Editorial Board member. The authors confirm that this does not alter their adherence to all the PLOS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. This figure shows the results of the genome-wide linkage scan for eGFR in population-specific and population-combined analysis that accounted the covariate effects of BMI and diabetes duration.
AA-African Americans; AI-American Indians; EA-European Americans; MA-Mexican Americans, cM-Centi Morgans.
Figure 2
Figure 2
Figure 2a. The figure shows the linkage of eGFR on 10p12 after accounting for the covariate effects of BMI and diabetes duration in the population-specific and combined analysis. A black dot denotes the location of rs1345561 (62.24 cM) that is associated with eGFR in African American participants (P  =  3.1 × 10−4) after accounting for the covariate effects of BMI and diabetes duration. AA-African Americans; AI-American Indians; EA-European Americans; MA-Mexican Americans, cM-Centi Morgans. Figure 2b.The figure shows the linkage of eGFR on 20q11 after accounting for the covariate effects of BMI and diabetes duration in the population-specific and combined analysis. The green and black dots denote the location of rs1885567 (43.47 cM) rs968478 (75.75 cM) that are associated with eGFR in MA (P  =  0034) and AA (P = 0.0018) respectively. AA-African Americans; AI-American Indians; EA-European Americans; MA-Mexican Americans; cM-Centi Morgans.
See this image and copyright information in PMC

References

    1. Rossing P, de Zeeuw D (2011) Need for better diabetes treatment for improved renal outcome. Kidney Int Suppl 120: S28–S32. - PubMed
    1. de Boer IH, Rue TC, Hall YN, Heagerty PJ, Weiss NS, et al. (2011) Temporal trends in the prevalence of diabetic kidney disease in the United States. JAMA 305: 2532–2539. - PMC - PubMed
    1. Nelson RG, Pettitt DJ, Carraher MJ, Baird HR, Knowler WC (1998) Effect of proteinuria on mortality in NIDDM. Diabetes 37: 1499–504. - PubMed
    1. Pavkov ME, Knowler WC, Lemley KV, Mason CC, Myers BD, et al. (2012) Early renal function decline in type 2 diabetes. Clin J Am Soc Nephrol 7: 78–84. - PMC - PubMed
    1. Hunt SC, Coon H, Hasstedt SJ, Cawthon RM, Camp NJ, et al. (2004) Linkage of serum creatinine and glomerular filtration rate to chromosome 2 in Utah pedigrees. Am J Hypertens 17: 511–515. - PubMed

Publication types