A genome-wide association study identifies two new risk loci for Graves' disease

Huai-Dong Song and colleagues report results of a genome-wide association study of Graves' disease. They confirm four previously reported risk loci for this disease and identify two new susceptibility loci at 4p14 and 6q27. 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.