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The autoimmune thyroid diseases (AITD), encompassing Graves' disease (GD) and Hashimoto's thyroiditis (HT), occur in genetically susceptible individuals. In order to identify the AITD susceptibility genes, we have studied DNA markers in the regions of 8 candidate genes: (1) the HLA region, (2) the TSH receptor, (3) thyroid peroxidase, (4) thyroglobulin, (5) IDDM-4, (6) IDDM-5, (7) Immunoglobulin heavy chain gene and (8) CTLA-4. One hundred and seven subjects from 19 informative families were studied, 14 subjects had GD and 32 subjects had HT. LOD scores were maximized assuming both dominant and recessive modes of inheritance. No linkage was found for any marker in patients with HT. In patients with GD, negative LOD scores were obtained for all the candidate genes, except for markers in the TSH receptor region on chromosome 14q31. Positive LOD scores were found for several markers on 14q31. Marker D14S81 gave the highest score (Z max = 2.05, theta = 0.01) assuming a dominant mode of inheritance and a penetrance of 0.8. These data confirm our previous observations of a lack of a necessary disease locus for AITD in the HLA gene region. Further, the data suggest the presence of an important susceptibility gene on 14q31 but at a considerable distance from the TSH receptor gene.

Mapping of a Major Susceptibility Locus for Graves’ Disease (GD-1) to Chromosome 14q31