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. 2009 Dec;3(1-4):77-82.
doi: 10.1007/s11568-010-9133-2. Epub 2010 Feb 24.

Targeted genome-wide investigation identifies novel SNPs associated with diabetic nephropathy

Amy Jayne McKnight, Diane Currie, Chris C Patterson, Alexander P Maxwell, Damian G Fogarty; Warren 3/UK GoKinD Study Group

Targeted genome-wide investigation identifies novel SNPs associated with diabetic nephropathy

Amy Jayne McKnight et al. Hugo J. 2009 Dec.

Abstract

Loci contributing to complex disease have been identified by focusing on genome-wide scans utilising non-synonymous single nucleotide polymorphisms (nsSNPs). We employed Illumina's HNS12 BeadChip (13,917 high-value SNPs) which was specifically designed to capture nsSNPs and ideally complements more dense genome-wide association studies that fail to consider many of these putatively functional variants. The HNS12 panel also includes 870 tag SNPs covering the major histocompatibility region. All individuals genotyped in this study were Caucasians with (cases) and without (controls) diabetic nephropathy. About 449 individuals with type 2 diabetes (203 cases, 246 controls) were genotyped in the initial study. 1,467 individuals with type 1 diabetes (718 cases, 749 controls) were genotyped in the follow up study. 11,152 SNPs were successfully analysed and ranked for association with diabetic nephropathy based on significance (P) values. The top ranked 32 SNPs were subsequently genotyped using MassARRAY iPLEX(™) and TaqMan technologies to investigate association of these polymorphisms with nephropathy in individuals with type 1 diabetes. The top ranked nsSNP, rs1543547 (P = 10(-5)), is located in RAET1L, a major histocompatibility class I-related gene at 6q25.1. Of particular interest, multiple nsSNPs within the top ranked (0.2%) SNPs are within several plausible candidate genes for nephropathy on 3q21.3 and 6p21.3.

Keywords: Diabetic nephropathy; Genetic predisposition; MHC; nsSNP.

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Figures

Fig. 1
Fig. 1
Log P values for each SNP genotyped per chromosome
See this image and copyright information in PMC

References

    1. Ansell D, Feehally J, Fogarty D, et al. UK Renal Registry Report 2008. Bristol, UK: UK Renal Registry; 2008.
    1. Barrett JC, Fry B, Maller J, Daly MJ, et al. Haploview: analysis and visualization of LD and haplotype maps. Bioinformatics. 2005;21:263–265. doi: 10.1093/bioinformatics/bth457. - DOI - PubMed
    1. Caramori ML, Mauer M. Diabetes and nephropathy. Curr Opin Nephrol Hypertens. 2003;12:273–282. doi: 10.1097/00041552-200305000-00008. - DOI - PubMed
    1. Clayton DG, Walker NM, Smyth DJ, et al. Population structure, differential bias and genomic control in a large-scale, case-control association study. Nat Genet. 2005;37:1243–1246. doi: 10.1038/ng1653. - DOI - PubMed
    1. de Bakker PI, Yelensky R, Pe’er I, et al. Efficiency and power in genetic association studies. Nat Genet. 2005;37:1217–1223. doi: 10.1038/ng1669. - DOI - PubMed