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

Genomewide linkage scan for diabetic renal failure and albuminuria: the FIND study

Robert P Igo Jr et al. Am J Nephrol. 2011.

Abstract

Background: Diabetic nephropathy (DN) is a leading cause of mortality and morbidity in patients with type 1 and type 2 diabetes. The multicenter FIND consortium aims to identify genes for DN and its associated quantitative traits, e.g. the urine albumin:creatinine ratio (ACR). Herein, the results of whole-genome linkage analysis and a sparse association scan for ACR and a dichotomous DN phenotype are reported in diabetic individuals.

Methods: A genomewide scan comprising more than 5,500 autosomal single nucleotide polymorphism markers (average spacing of 0.6 cM) was performed on 1,235 nuclear and extended pedigrees (3,972 diabetic participants) ascertained for DN from African-American (AA), American-Indian (AI), European-American (EA) and Mexican-American (MA) populations.

Results: Strong evidence for linkage to DN was detected on chromosome 6p (p = 8.0 × 10(-5), LOD = 3.09) in EA families as well as suggestive evidence for linkage to chromosome 7p in AI families. Regions on chromosomes 3p in AA, 7q in EA, 16q in AA and 22q in MA displayed suggestive evidence of linkage for urine ACR. The linkage peak on chromosome 22q overlaps the MYH9/APOL1 gene region, previously implicated in AA diabetic and nondiabetic nephropathies.

Conclusion: These results strengthen the evidence for previously identified genomic regions and implicate several novel loci potentially involved in the pathogenesis of DN.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Autosomal genomewide model-free linkage scan for DN. From top to bottom, panels display results for AA, AI, EA and MA samples, as well as pooled Fisher p values from all study samples (All).
Fig. 2
Fig. 2
Detailed linkage and association results for DN for segments of chromosomes 6 (a), 7 (b), 18 (c, e) and 22 (d, f, g). Heavy lines trace linkage results for AA, AI, EA and MA samples, as well as combined Fisher p values (alternating dots and dashes). Tick marks at the top show the location of Illumina IV SNPs. In panel e, results from association analysis for AI (·) are shown along with the linkage profile from panel c. In panels f and g, association results for AI and EA are shown (·), respectively, with the linkage profiles from panel d.
Fig. 3
Fig. 3
Genomewide linkage scan for ACR, adjusted for sex and age at DM diagnosis. See legend of fig. 1 for explanation of plots and symbols.
Fig. 4
Fig. 4
Detailed linkage and association results for ACR, on segments of chromosomes 3 (a), 7 (b), 21 (c, e) and 22 (d). Axes and lines are as in figure 2. In panel e, results from association analysis for the AA sample are shown (·) with the AA linkage profile from panel c.
See this image and copyright information in PMC

References

    1. Collins AJ, Foley RN, Herzog C, Chavers B, Gilbertson D, Ishani A, Kasiske B, Liu J, Mau LW, McBean M, Murray A, St Peter W, Guo H, Gustafson S, Li Q, Li S, Li S, Peng Y, Qiu Y, Roberts T, Skeans M, Snyder J, Solid C, Wang C, Weinhandl E, Zaun D, Arko C, Chen S-C, Dalleska F, Daniels F, Dunning S, Ebben J, Frazier E, Hanzlik C, Johnson R, Sheets D, Wang X, Forrest B, Constantini E, Everson S, Eggers P, Agodoa L. US Renal data system 2010 annual report. Am J Kidney Dis. 2011;57(suppl 1):e1–e526. - PubMed
    1. Dinneen SF, Gerstein HC. The association of microalbuminuria and mortality in non-insulin-dependent diabetes mellitus. A systematic overview of the literature. Arch Int Med. 1997;157:1413–1418. - PubMed
    1. Goodkin DA, Bragg-Gresham JL, Koenig KG, Wolfe RA, Akiba T, Andreucci VE, Saito A, Rayner HC, Kurokawa K, Port FK, Held PJ, Young EW. Association of comorbid conditions and mortality in hemodialysis patients in Europe, Japan, and the United States: the Dialysis Outcomes and Practice Patterns Study (DOPPS) J Am Soc Nephrol. 2003;14:3270–3277. - PubMed
    1. Freedman BI, Bostrom M, Daeihagh P, Bowden DW. Genetic factors in diabetic nephropathy. Clin J Am Soc Nephrol. 2007;2:1306–1316. - PubMed
    1. Maeda S. Genetics of diabetic nephropathy. Ther Adv Cardiovasc Dis. 2008;2:363–371. - PubMed

Publication types

Grants and funding