Genomewide linkage scan for diabetic renal failure and albuminuria: The find study

Robert P. Igo, Sudha K. Iyengar, Susanne B. Nicholas, Katrina A.B. Goddard, Carl D. Langefeld, Robert L. Hanson, Ravindranath Duggirala, Jasmin Divers, Hanna Abboud, Sharon G. Adler, Nedal H. Arar, Amanda Horvath, Robert C. Elston, Donald W. Bowden, Xiuqing Guo, Eli Ipp, W. H.Linda Kao, Paul L. Kimmel, William C. Knowler, Lucy A. MeoniJulio Molineros, Robert G. Nelson, Madeline V. Pahl, Rulan S. Parekh, Rebekah S. Rasooly, Jeffrey R. Schelling, Vallabh O. Shah, Michael W. Smith, Cheryl A. Winkler, Philip G. Zager, John R. Sedor, Barry I. Freedman

Research output: Contribution to journalArticle

40 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)381-389
Number of pages9
JournalAmerican journal of nephrology
Volume33
Issue number5
DOIs
StatePublished - May 2011

Keywords

  • Albuminuria
  • Allelic association
  • Diabetes mellitus
  • End-stage renal disease
  • Linkage
  • Renal failure

ASJC Scopus subject areas

  • Nephrology

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    Igo, R. P., Iyengar, S. K., Nicholas, S. B., Goddard, K. A. B., Langefeld, C. D., Hanson, R. L., Duggirala, R., Divers, J., Abboud, H., Adler, S. G., Arar, N. H., Horvath, A., Elston, R. C., Bowden, D. W., Guo, X., Ipp, E., Kao, W. H. L., Kimmel, P. L., Knowler, W. C., ... Freedman, B. I. (2011). Genomewide linkage scan for diabetic renal failure and albuminuria: The find study. American journal of nephrology, 33(5), 381-389. https://doi.org/10.1159/000326763