Evidence for a new Graves disease susceptibility locus at chromosome 18q21

Graves disease (GD) is a common autoimmune thyroid disorder that is inherit ed as a complex multigenic trait. By using a single microsatellite marker a t each locus, we screened the type 1 diabetes loci IDDM4 IDDM5, IDDM6, IDDM 8, and IDDM10 and the fucosyltransferase-2 locus for linkage in sib pairs w ith GD. This showed a two-point nonparametric linkage (NPL) score of 1.57 ( P = .06) at the IDDM6 marker D18S41, but NPL scores were <1.0 at the other five loci. Thus, the investigation of the IDDM6 locus was extended by genot yping 11 microsatellite markers spanning 48 cM across chromosome 18q12-q22 in 81 sib pairs affected with autoimmune thyroid disease (AITD). Multipoint analysis, designating all AITD sib pairs as affected, showed a peak NPL sc ore of 3.46 (P = .0003), at the marker D18S487. Designation of only GD case s as affected (74 sib pairs) showed a peak NPL score of 3.09 (P = .001). Li nkage to this region has been demonstrated in type 1 diabetes (IDDM6), rheu matoid arthritis, and systemic lupus erythematosus, which suggests that thi s locus may have a role in several forms of autoimmunity.