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Remapping the type I diabetes association of the CTLA4 locus

Genes & Immunity volume 10, pages S27–S32 (2009)Cite this article

Abstract

The Type I Diabetes Genetics Consortium genotyped 24 single-nucleotide polymorphisms (SNPs) in the CTLA4 locus in 2298 type I diabetes (T1D) nuclear families (11 159 individuals, 5003 affected) to evaluate the recognized T1D association. The 24 CTLA4 SNPs span ∼43 kb from the 5′ flanking to 3′ flanking region of the gene in the middle of an extended region of linkage disequilibrium of more than 100 kb. The genotyping was performed using two technologies (Illumina GoldenGate and Sequenom iPlex) on the same samples. The genotype calls by both the methods were highly consistent (the majority >99%). Previously reported T1D association from both the +49G>A and the CT60 SNPs was replicated. The reported association of the −319C>T SNP was not replicated. Although associated with T1D risk, it is likely that neither SNP is causative, as the peak of T1D association was from the SNP rs231727 at 3′ flanking of the CTLA4 gene. Comprehensive resequencing and fine mapping of the CTLA4 region are still needed to clarify the causal variants.

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Acknowledgements

The Type I Diabetes Genetics Consortium (T1DGC) is funded by the NIH Grant U01-DK62418. The GWAS from our group was funded by the Children's Hospital of Philadelphia, the Juvenile Diabetes Research Foundation International and Genome Canada. We thank all the patients and the healthy control subjects for their participation in the study. HQQ is supported by a fellowship from the Canadian Institutes of Health Research. Special thanks for the helpful comments from Dr John Todd. 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. Department of Pediatrics, McGill University, Montreal, Québec, Canada

    H-Q Qu & C Polychronakos

  2. Department of Human Genetics, McGill University, Montreal, Québec, Canada

    H-Q Qu & C Polychronakos

  3. 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

  4. 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., Grant, S. et al. Remapping the type I diabetes association of the CTLA4 locus. Genes Immun 10 (Suppl 1), S27–S32 (2009). https://doi.org/10.1038/gene.2009.88

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