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Objective Associations between IL2 RA and various autoimmune diseases have been reported in Caucasians. We investigated whether genetic polymorphisms at the IL2 RA locus were associated with Graves' disease ( GD) in the Chinese Han population. Design We performed a genome-wide association study ( GWAS) in 1 536 GD patients and 1 516 controls. The 1000 Genomes Project data were adopted as references for imputation analysis. After forward and conditional logistic regressions, we found that rs11256313 was the major risk variant in the CD25/ IL2 RA region. Thus, we further genotyped rs11256313 in a replication cohort with 3 694 GD patients and 3 510 controls using ABI 7900 HT TaqMan Real-Time PCR System. Results Nine single nucleotide polymorphisms ( SNPs) in the IL2 RA block were nominally associated with GD in our GWAS (0·01 < P < 0·05). After imputation analysis, 13 imputed SNPs in the IL2 RA block were weakly associated with GD ( P ≤ 0·05). Logistic regression analysis suggested that the imputed rs11256313 could represent the IL2 RA block ( P = 0·003). However, we failed to replicate the association of rs11256313 in a larger cohort ( P = 0·145). A subphenotype analysis of rs11256313 on thyroid hormone receptor antibody ( TRAb) and gender showed that there was no association in any of the subphenotype groups ( P > 0·05). Conclusions The results suggested that common genetic polymorphisms at IL2 RA do not exert a significant genetic effect on the development of GD in the Chinese Han population. Previously reported associations between CD25/ IL2 RA and autoimmune diseases including GD in Caucasians again imply that heterogeneity exists in different ethnic populations. [ABSTRACT FROM AUTHOR]

Graves' disease is a common autoimmune disorder characterized by thyroid stimulating hormone receptor autoantibodies (TRAb) and hyperthyroidism. To investigate the genetic architecture of Graves' disease, we conducted a genome-wide association study in 1,536 individuals with Graves' disease (cases) and 1,516 controls. We further evaluated a group of associated SNPs in a second set of 3,994 cases and 3,510 controls. We confirmed four previously reported loci (in the major histocompatibility complex, TSHR, CTLA4 and FCRL3) and identified two new susceptibility loci (the RNASET2-FGFR1OP-CCR6 region at 6q27 (P(combined) = 6.85 × 10(-10) for rs9355610) and an intergenic region at 4p14 (P(combined) = 1.08 × 10(-13) for rs6832151)). These newly associated SNPs were correlated with the expression levels of RNASET2 at 6q27, of CHRNA9 and of a previously uncharacterized gene at 4p14, respectively. Moreover, we identified strong associations of TSHR and major histocompatibility complex class II variants with persistently TRAb-positive Graves' disease.