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- Title
Association of the TSHR gene with Graves' disease: the first disease specific locus.
- Authors
Dechairo, Bryan M.; Zabaneh, Delilah; Collins, Joanne; Brand, Oliver; Dawson, Gary J.; Green, Angie P.; Mackay, Ian; Franklyn, Jayne A.; Connell, John M.; Wass, John A. H.; Wiersinga, Wilmar M.; Hegedus, Laszlo; Brix, Thomas; Robinson, Bruce G.; Hunt, Penny J.; Weetman, Anthony P.; Carey, Alisoun H.; Gough, Stephen C.
- Abstract
The development of autoimmune thyroid disease (AITD) is associated with autoantibodies directed against the thyroid stimulating hormone receptor (TSHR). Previous studies have failed to demonstrate a consistent association between the TSHR and AITD, or any of its sub-phenotypes. In the present study, we analysed the linkage disequilibrium (LD) structure encompassing the TSHR, to identify LD ‘blocks’ and SNPs, which capture the majority of intra-block haplotype diversity. The haplotype tagging SNPs, plus all common SNPs reported in previous studies were genotyped in 1059 AITD Caucasian cases and 971 Caucasian controls. A haplotype, across two LD blocks, showed association (P<1 × 10−6, OR 1.7) with Graves’ disease (GD) but not autoimmune hypothyroidism (AIH). We replicated these findings by genotyping the most associated GD SNP, rs2268458, in a separate UK Caucasian cohort of 1366 AITD cases and 1061 controls (GD, P=2 × 10−6, OR 1.3; AIH, P=NS). These results in two independent Caucasian data sets suggest that the TSHR is the first replicated GD-specific locus meriting further fine mapping and functional analysis to identify the aetiological variants.European Journal of Human Genetics (2005) 13, 1223–1230. doi:10.1038/sj.ejhg.5201485; published online 17 August 2005
- Subjects
AUTOIMMUNE diseases; THYROID diseases; AUTOANTIBODIES; THYROTROPIN; GENETICS; GLYCOPROTEIN hormones; IMMUNOGLOBULINS
- Publication
European Journal of Human Genetics, 2005, Vol 13, Issue 11, p1223
- ISSN
1018-4813
- Publication type
Article
- DOI
10.1038/sj.ejhg.5201485