Regression mapping of association between the human leukocyte antigen region and Graves disease

Matthew J. Simmonds, Joanna M.M. Howson, Joanne M. Heward, Heather J. Cordell, Helen Foxall, Jackie Carr-Smith, Sarah M. Gibson, Neil Walker, Yaron Tomer, Jayne A. Franklyn, John A. Todd, Stephen C.L. Gough

Research output: Contribution to journalArticlepeer-review

125 Scopus citations


The human leukocyte antigen class II genes DRB1, DQB1, and DQA1 are associated with Graves disease (GD), but, because of strong linkage disequilibrium within this region, the primary etiological variant(s) remains unknown. In the present study, 871 patients with GD and 621 control subjects were genotyped at the DRB1, DQB1, and DQA1 loci. All three loci were associated with GD (P = 1.45 × 10-12, P = 3.20 × 10-5, and P = 9.26 × 10-12, respectively). Stepwise logistic-regression analysis showed that the association could be explained by either DRB1 or DQA1 but not by DQB1. To extend previous results, the amino acid sequence of the exon 2-encoded peptide-binding domain of DRB1 was predicted for each subject, and, by use of logistic regression, each position was analyzed for association with GD. Of 102 amino acids, 70 were uninformative; of the remaining 32 amino acids, 13 were associated with GD (P values ranged from 2.20 × 10-4 to 1.2 × 10-12). The strongest association was at position β74. This analysis is consistent with the possibility that position β74 of exon 2 of the DRB1 molecule may have a specific and central role in autoantigen presentation by DRB1 to T lymphocytes. However, we cannot yet exclude a primary role for DQA1 or for other polymorphisms that affect DRB1 function or expression.

Original languageEnglish (US)
Pages (from-to)157-163
Number of pages7
JournalAmerican Journal of Human Genetics
Issue number1
StatePublished - Jan 2005
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


Dive into the research topics of 'Regression mapping of association between the human leukocyte antigen region and Graves disease'. Together they form a unique fingerprint.

Cite this