Large-scale genetic fine mapping and genotype-phenotype associations implicate polymorphism in the IL2RA region in type 1 diabetes View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2007-09

AUTHORS

Christopher E Lowe, Jason D Cooper, Todd Brusko, Neil M Walker, Deborah J Smyth, Rebecca Bailey, Kirsi Bourget, Vincent Plagnol, Sarah Field, Mark Atkinson, David G Clayton, Linda S Wicker, John A Todd

ABSTRACT

Genome-wide association studies are now identifying disease-associated chromosome regions. However, even after convincing replication, the localization of the causal variant(s) requires comprehensive resequencing, extensive genotyping and statistical analyses in large sample sets leading to targeted functional studies. Here, we have localized the type 1 diabetes (T1D) association in the interleukin 2 receptor alpha (IL2RA) gene region to two independent groups of SNPs, spanning overlapping regions of 14 and 40 kb, encompassing IL2RA intron 1 and the 5' regions of IL2RA and RBM17 (odds ratio = 2.04, 95% confidence interval = 1.70-2.45; P = 1.92 x 10(-28); control frequency = 0.635). Furthermore, we have associated IL2RA T1D susceptibility genotypes with lower circulating levels of the biomarker, soluble IL-2RA (P = 6.28 x 10(-28)), suggesting that an inherited lower immune responsiveness predisposes to T1D. More... »

PAGES

1074-1082

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/ng2102

    DOI

    http://dx.doi.org/10.1038/ng2102

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1017373644

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/17676041


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