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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. © 2005 Nature Publishing Group. All rights reserved.
Dechairo, B. M., Zabaneh, D., Collins, J., Brand, O., Dawson, G. J., Green, A. P., … Gough, S. C. (2005). Association of the TSHR gene with Graves’ disease: The first disease specific locus. European Journal of Human Genetics, 13(11), 1223–1230. https://doi.org/10.1038/sj.ejhg.5201485