The classical human leukocyte antigen (HLA) genes were the most important genetic determinant for Graves’ disease (GD). We applied imputation to thoroughly investigate the MHC associations with GD down to the amino acid level of classical HLA genes in 1,468 GD patients and 1,490 controls of Han Chinese. We observed the top association signal at HLA-DPβ1 position 205 and HLA-DPA1*02:02 was the strongest association among the classical HLA alleles, which was in perfect LD with HLA-DPα1 residue Met11. Conditional analysis revealed four amino acid positions could account for most HLA association with GD in Han Chinese. HLA-DPα1 Met11 might explain the risk heterogeneity between two clinical subtypes of GD, namely persistent TRAb positive (pTRAb+) group after anti-thyroid drug therapy and “non-persistent TRAb positive” (pTRAb-) group after ATD therapy. (By Dr. Xun Chu, https://jmg.bmj.com/content/early/2018/07/09/jmedgenet-2017-105146 )

The most strongly associated amino acid positions of classical HLA genes with Graves’ disease susceptibility in Han Chinese