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

©� 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 � ,536 individuals with Graves’ disease (cases) and � ,5�6 controls. We further evaluated a group of associated SNPs in a second set of 3,994 cases and 3,5�0 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 × � 0 − �0 for rs93556�0) and an intergenic region at 4p�4 (Pcombined = � .08 × � 0 − �3 for rs6832�5�)). These newly associated SNPs were correlated with the expression levels of RNASET2 at 6q27, of CHRNA9 and of a previously uncharacterized gene at 4p�4, respectively. Moreover, we identified strong associations of TSHR and major histocompatibility complex class II variants with persistently TRAb-positive Graves’ disease.