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. 2005 May;76(5):773-9.
doi: 10.1086/429843. Epub 2005 Mar 17.

Localization of a type 1 diabetes locus in the IL2RA/CD25 region by use of tag single-nucleotide polymorphisms

Adrian Vella  1 , Jason D Cooper, Christopher E Lowe, Neil Walker, Sarah Nutland, Barry Widmer, Richard Jones, Susan M Ring, Wendy McArdle, Marcus E Pembrey, David P Strachan, David B Dunger, Rebecca C J Twells, David G Clayton, John A Todd
Affiliations

Localization of a type 1 diabetes locus in the IL2RA/CD25 region by use of tag single-nucleotide polymorphisms

Adrian Vella et al. Am J Hum Genet. 2005 May.

Abstract

As part of an ongoing search for genes associated with type 1 diabetes (T1D), a common autoimmune disease, we tested the biological candidate gene IL2RA (CD25), which encodes a subunit (IL-2R alpha) of the high-affinity interleukin-2 (IL-2) receptor complex. We employed a tag single-nucleotide polymorphism (tag SNP) approach in large T1D sample collections consisting of 7,457 cases and controls and 725 multiplex families. Tag SNPs were analyzed using a multilocus test to provide a regional test for association. We found strong statistical evidence in the case-control collection (P=6.5x10(-8)) for a T1D locus in the CD25 region of chromosome 10p15 and replicated the association in the family collection (P=7.3x10(-3); combined P=1.3x10(-10)). These results illustrate the utility of tag SNPs in a chromosome-regional test of disease association and justify future fine mapping of the causal variant in the region.

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Figures

Figure 1
Figure 1
Upper panel, Odds ratios and transmission ratios for the minor allele of CD25 tag SNPs genotyped in the case-control (filled circles) and family (open circles) collections, respectively. Vertical lines indicate 95% CIs. Lower panel, Chromosome position of CD25 tag SNPs. Open long rectangle indicates UTR, filled long rectangles indicate exons, filled short rectangles indicate regulatory regions, and the arrow labeled “+1” indicates the transcript start site. A version of this figure can be viewed at the T1DBase Web site.
See this image and copyright information in PMC

References

Electronic-Database Information

    1. dbSNP Home Page, http://www.ncbi.nlm.nih.gov/SNP/index.html
    1. D.G.C.'s Web site, http://www-gene.cimr.cam.ac.uk/clayton/software/ (for the programs used for the selection and analysis of tag SNPs)
    1. Fondation Jean Dausset–CEPH, http://www.cephb.fr/ (for information about the individuals used in the sequencing panel)
    1. Juvenile Diabetes Research Foundation/Wellcome Trust, http://www-gene.cimr.cam.ac.uk/todd/dna-refs.shtml (for references to DNA collections used at the Juvenile Diabetes Research Foundation/Wellcome Trust Diabetes and Inflammation Laboratory)
    1. National Center for Biotechnology Information (NCBI), http://www.ncbi.nlm.nih.gov/

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