4.3 Review

Insights to the Genetics of Diabetic Nephropathy Through a Genome-Wide Association Study of the GoKinD Collection

Journal

SEMINARS IN NEPHROLOGY
Volume 30, Issue 2, Pages 126-140

Publisher

W B SAUNDERS CO-ELSEVIER INC
DOI: 10.1016/j.semnephrol.2010.01.004

Keywords

Genome-wide association; diabetic nephropathy; type 1 diabetes; imputation

Funding

  1. National Institutes of Health [DK77532, T32 DK007260-31]
  2. Juvenile Diabetes Research Foundation [3-2009-397]
  3. Centers for Disease Control (CDC) [PL 105-33, 106-554, 107-360]
  4. NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK036836, R01DK077532, T32DK007260] Funding Source: NIH RePORTER

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The Genetics of Kidneys in Diabetes (Go KinD) study was initiated to facilitate research aimed at identifying genes involved in diabetic nephropathy (DN) in type 1 diabetes. In this review, we present an overview of this study and the various reports that have used its collection. At the forefront of these efforts is the recent genome-wide association scan implemented on the Go KinD collection. We highlight the results from our analysis of these data and describe compelling evidence from animal models that further support the potential role of associated loci in the susceptibility of DN. To enhance our analysis of genetic associations in GoKinD, using genome-wide imputation, we expanded our analysis of this collection to include genotype data from more than 2.4 million common single nucleotide polymorphisms. We illustrate the added utility of this enhanced dataset through the comprehensive fine-mapping of candidate genomic regions previously linked with DN and the targeted investigation of genes involved in candidate pathways implicated in its pathogenesis. Collectively, genome-wide association and genome-wide imputation data from the GoKinD collection will serve as a springboard for future investigations into the genetic basis of DN in type 1 diabetes. Semin Nephrol 30:126-140 (C) 2010 Elsevier Inc. All rights reserved.

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