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

被引：312

作者：

Lowe, Christopher E.

Cooper, Jason D.

Brusko, Todd

Walker, Neil M.

Smyth, Deborah J.

Bailey, Rebecca

Bourget, Kirsi

Plagnol, Vincent

Field, Sarah

Atkinson, Mark

Clayton, David G.

Wicker, Linda S.

Todd, John A. ^{[1
]}

机构：

[1] Univ Cambridge, Addenbrookes Hosp, Juvenile Diabet Res Fdn,Cambridge Inst Med Res, Wellcome Trust Diabet & Inflammat Lab,Dept Med Ge, Cambridge CB2 0XY, England

[2] Univ Florida, Coll Med, Gainesville, FL 32610 USA

来源：

NATURE GENETICS | 2007年 / 39卷 / 09期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

D O I：

10.1038/ng2102

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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.

引用

页码：1074 / 1082

页数：9

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