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The type I diabetes association of the IL2RA locus

Genes & Immunity volume 10, pages S42–S48 (2009)Cite this article

Abstract

To confirm and fine map previous reports of association, the Type I Diabetes (T1D) Genetics Consortium (T1DGC) assembled a large collection of DNA samples from affected sib-pair (ASP) families with T1D (5003 affected individuals) and genotyped polymorphic markers. One of these loci, involving the IL2RA gene, had been reported to be due to three independent effects. The T1DGC genotyped 69 single-nucleotide polymorphisms (SNPs) that span ∼88 kb from the 5′ flanking to 3′ flanking region of the IL2RA locus. The most highly associated SNP reported earlier (ss52580101) was not included in the genotyping list; however, a 5-SNP (rs3134883, rs3118470, rs7072793, rs4749955 and rs12251307) haplotype (H5) was identified that strongly tagged its minor allele with r2=0.869 (95% CI, 0.850–0.885). This haplotype was significantly protective (P=3.2 × 10−5) in the T1D ASP families, with an odds ratio virtually identical to that reported for ss52580101. The SNP marking the second independent locus, (rs11594656) showed no association in the T1DGC set and the third (rs2104286) could not be distinguished, by conditional regression, from H5. Instead, the most significant independent effect was detected from the 5′ flanking IL2RA SNP rs4749955, which remained significant after regression for H5. Thus, we confirm independent effects at the IL2RA locus.

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Acknowledgements

The Type I Diabetes Genetics Consortium (T1DGC) is funded by the NIH Grant U01-DK62418. This study was additionally funded by the Juvenile Diabetes Research Foundation International, Genome Canada and the Children's Hospital of Philadelphia. We thank all the T1D families for their participation in the study. HQQ is supported by a fellowship from the Canadian Institutes of Health Research. Special thanks for helpful discussion and comments from Joanna Howson. Genotyping was performed at the Broad Institute Center for Genotyping and Analysis is supported by grant U54 RR020278 from the National Center for Research Resources.

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Authors and Affiliations

  1. Endocrine Genetics Laboratory, The McGill University Health Center (Montreal Children's Hospital), Montréal, Québec, Canada

    H-Q Qu & C Polychronakos

  2. Center for Applied Genomics, Abramson Research Center, The Children's Hospital of Philadelphia, Philadelphia, PA, USA

    J P Bradfield, S F A Grant & H Hakonarson

  3. McGill University, Montréal, Québec, Canada

    A Bélisle

  4. Genome Québec Innovation Centre, Montréal, Québec, Canada

    A Bélisle

  5. Division of Human Genetics, Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA

    S F A Grant & H Hakonarson

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Correspondence to C Polychronakos.

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Qu, HQ., Bradfield, J., Bélisle, A. et al. The type I diabetes association of the IL2RA locus. Genes Immun 10 (Suppl 1), S42–S48 (2009). https://doi.org/10.1038/gene.2009.90

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