Evidence for a new Graves disease susceptibility locus at chromosome 18q21.
Graves disease (GD) is a common autoimmune thyroid disorder that is inherited as a complex multigenic trait. By using a single microsatellite marker at each locus, we screened the type 1 diabetes loci IDDM4, IDDM5, IDDM6, IDDM8, and IDDM10 and the fucosyltransferase-2 locus for linkage in sib pairs with 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 genotyping 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 score of 3.46 (P=.0003), at the marker D18S487. Designation of only GD cases as affected (74 sib pairs) showed a peak NPL score of 3.09 (P=.001). Linkage to this region has been demonstrated in type 1 diabetes (IDDM6), rheumatoid arthritis, and systemic lupus erythematosus, which suggests that this locus may have a role in several forms of autoimmunity.
Vaidya
B
B
Department of Endocrinology, School of Clinical Medical Sciences, University of Newcastle upon Tyne, Newcastle upon Tyne, NE2 4HH, United Kingdom. bvaidya@hgmp.mrc.ac.uk.
Imrie
H
H
Perros
P
P
Young
E T
ET
Kelly
W F
WF
Carr
D
D
Large
D M
DM
Toft
A D
AD
Kendall-Taylor
P
P
Pearce
S H
SH
D000483:Alleles; D002874:Chromosome Mapping; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D005260:Female; D005647:Fucosyltransferases / Q000235:genetics; D018740:Genetic Heterogeneity; D008040:Genetic Linkage / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006111:Graves Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D016555:Matched-Pair Analysis; D018895:Microsatellite Repeats / Q000235:genetics; D008957:Models, Genetic; D009679:Nuclear Family; D010641:Phenotype; D018709:Statistics, Nonparametric; D013967:Thyroiditis, Autoimmune / Q000235:genetics; D044465:White People / Q000235:genetics; D000097631:Galactoside 2-alpha-L-fucosyltransferase
D005647:Fucosyltransferases; D000097631:Galactoside 2-alpha-L-fucosyltransferase