A new Graves disease-susceptibility locus maps to chromosome 20q11.2

The autoimmune thyroid diseases (AITDs) include two related disorders, Crav es disease (CD) 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 polymorphi c and densely spaced microsatellite markers (intermarker distance <10 cM). Linkage analysis was performed by use of two-point and multipoint parametri c methods (classic LOD-score analysis). While studying chromosome 20, we fo und 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 rece ssive 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 D20 S195. 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 fo r heterogeneity in our sample. In our view, these results indicate strong e vidence for linkage and suggest the presence of a major CD-susceptibility g ene on chromosome 20q11.2.