A New Graves Disease-Susceptibility Locus Maps to Chromosome 20q11.2. International Consortium for the Genetics of Autoimmune Thyroid Disease

Am J Hum Genet. 1998 Dec;63(6):1749-56. doi: 10.1086/302146.


The autoimmune thyroid diseases (AITDs) include two related disorders, Graves disease (GD) and Hashimoto thyroiditis, in which perturbations of immune regulation result in an immune attack on the thyroid gland. The AITDs are multifactorial and develop in genetically susceptible individuals. However, the genes responsible for this susceptibility remain unknown. Recently, we initiated a whole-genome linkage study of patients with AITD, in order to identify their susceptibility genes. We studied a data set of 53 multiplex, multigenerational AITD families (323 individuals), using highly polymorphic and densely spaced microsatellite markers (intermarker distance <10 cM). Linkage analysis was performed by use of two-point and multipoint parametric methods (classic LOD-score analysis). While studying chromosome 20, we found a locus on chromosome 20q11.2 that was strongly linked to GD. A maximum two-point LOD score of 3.2 was obtained at marker D20S195, assuming a recessive mode of inheritance and a penetrance of.3. The maximum nonparametric LOD score was 2.4 (P=.00043); this score also was obtained at marker D20S195. Multipoint linkage analysis yielded a maximum LOD score of 3.5 for a 6-cM interval between markers D20S195 and D20S107. There was no evidence for heterogeneity in our sample. In our view, these results indicate strong evidence for linkage and suggest the presence of a major GD-susceptibility gene on chromosome 20q11.2.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Autoantibodies / analysis
  • Chromosome Mapping
  • Chromosomes, Human, Pair 20 / genetics*
  • Europe
  • Family Health
  • Female
  • Genetic Heterogeneity
  • Genetic Predisposition to Disease*
  • Graves Disease / genetics*
  • Graves Disease / immunology
  • Humans
  • Lod Score
  • Male
  • Microsatellite Repeats / genetics
  • Models, Genetic
  • North America
  • Penetrance
  • Sex Ratio
  • Thyroiditis, Autoimmune / genetics*
  • Thyroiditis, Autoimmune / immunology


  • Autoantibodies