Large-scale genetic fine mapping and genotype-phenotype associations implicate polymorphism in the IL2RA region in type 1 diabetes
作者： Christopher E Lowe , Jason D Cooper , Todd Brusko , Neil M Walker , Deborah J Smyth
DOI: 10.1038/NG2102
关键词:
摘要: Genome-wide association studies are now identifying disease-associated chromosome regions. However, even after convincing replication, the localization of causal variant(s) requires comprehensive resequencing, extensive genotyping and statistical analyses in large sample sets leading to targeted functional studies. Here, we have localized type 1 diabetes (T1D) interleukin 2 receptor alpha (IL2RA) gene region two independent groups SNPs, spanning overlapping regions 14 40 kb, encompassing IL2RA intron 5′ RBM17 (odds ratio = 2.04, 95% confidence interval 1.70–2.45; P 1.92 × 10−28; control frequency 0.635). Furthermore, associated T1D susceptibility genotypes with lower circulating levels biomarker, soluble IL-2RA (P 6.28 10−28), suggesting that an inherited immune responsiveness predisposes T1D.
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