Linkage analysis of candidate genes in autoimmune thyroid disease: 1. Selected immunoregulatory genes

Giuseppe Barbesino, Yaron Tomer, Erlinda Concepcion, Terry F. Davies, David A. Greenberg, Rhoda Cobin, Luca Chiovato, Aldo Pinchera, Sandra McLachlan, Bernard Rees Smith, Fred Clark, Eric Young, Meir Berezin

Research output: Contribution to journalArticlepeer-review

65 Scopus citations


Graves' and Hashimoto's diseases are autoimmune thyroid diseases in which the genetic contribution is complex. For this reason, identification of necessary susceptibility genes has been difficult. However, a number of immunoregulatory genes have been implicated by association studies, including: CTLA-4, a recently described protein involved in antigen presentation, located on chromosome 2q33; the T-cell receptor Vα and Vβ gene complexes, located on 14q11 and 7q35, respectively; end the Ig gene complex (IgH), located on 15q11. We used polymorphic microsatellite markers located within these genes, or gene complexes, to test for linkage (rather than association), to each of these candidates. Using markers within the loci allowed us to assume a fixed recombination fraction of 0.01 in the tested model. Three hundred eight subjects from 48 multiplex families were studied, with 142 affected subjects. Using this set of families, we have previously shown evidence of linkage with a major susceptibility locus for Graves' disease (GD-1) on 14q24.3-31, with a maximum lod (logarithm + odds) score of 2.1, at a penetrance of 80% and with a dominant mode of inheritance. In the present study, we obtained consistently negative lod scores for each of the candidate genes, assuming either dominant or recessive modes of inheritance. These data, therefore, showed evidence against linkage with all the candidate genes. Unlike association studies, linkage analyses detect major genetic influences on disease susceptibility exerted by the linked loci. The lack of linkage for the immunoregulatory genes that were studied indicated, therefore, that they were not major contributors to disease etiology.

Original languageEnglish (US)
Pages (from-to)1580-1584
Number of pages5
JournalJournal of Clinical Endocrinology and Metabolism
Issue number5
StatePublished - 1998
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical


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