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 (Pcombined = 6.85 × 10−10 for rs9355610) and an intergenic region at 4p14 (Pcombined = 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.
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We thank all subjects for participating in this study. This work was supported in part by the National Natural Science Foundation of China (30971595, 30971383 and 31000556), Chinese National Natural Science Fund for Distinguished Young Scholars (30625019), Chinese High-Tech Program (2007AA02Z175 and 2009AA022709), Shanghai Science and Technology Committee (10JC1410400, 09DZ2291900, 09JC1411300 and 10ZR1421400) and Program for Innovative Research Team of Shanghai Municipal Education Committee.
The author declare no competing financial interests.
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The China Consortium for the Genetics of Autoimmune Thyroid Disease. A genome-wide association study identifies two new risk loci for Graves' disease. Nat Genet 43, 897–901 (2011). https://doi.org/10.1038/ng.898
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