Fine mapping of thyroglobulin gene identifies two independent risk loci for Graves’ disease in Chinese Han population

Abstract

Background: This study aimed to determine independent risk loci of Graves' disease (GD) in the thyroglobulin (TG) region.Methods: In this two-staged association study, a total of 9,757 patients with GD and 10,626 sex-matched controls were recruited from Chinese Han population. Illumina Human660-Quad BeadChips in the discovery stage and TaqMan SNP Genotyping Assays in the replication stage were used for genotyping.Trend test and logistic regression analysis were performed in this association study.Results: In the discovery stage, rs2294025 and rs7005834 were the most highly associated susceptibility loci with GD in TG. In the replication phase, 7 SNPs, including rs2294025 and rs7005834, were selected for fine-mapping. Finally, we confirmed that rs2294025 and rs7005834 were the independent risk loci of GD in the combined populations. At the same time, there was no significant difference between the risk allele frequencies of rs2294025 and rs7005834 in different clinical phenotypes of GD. Conclusions:The fine mapping study of thyroglobulin identified two independent SNPs (rs2294025 and rs7005834) for GD susceptibility. However, no significant differences for rs2294025 and rs7005834 were observed, between the different clinical phenotypes of GD, including gender, Graves' ophthalmopathy (GO), and serum levels of thyrotropin receptor antibody, thyroid peroxidase antibody, and thyroglobulin antibody.These results provide a deeper understanding of the association mechanism of thyroglobulin and GD risk.

Global view on the pathogenesis of benign thyroid disease based on historical, experimental, biochemical and genetic data, identifying the role of magnesium, selenium, coenzyme Q10 and iron in the context of the unfolded protein response and protein quality control of thyroglobulin

“…In a study that looked at a group of Chinese Han subjects, two independent SNPs (rs2294025 and rs7005834) for Graves' disease susceptibility were described. Unfortunately, they showed no correlation with clinical phenotypes [80] .…”

Genetics, Epigenetics, Cellular Immunology, and Gut Microbiota: Emerging Links With Graves’ Disease

“…TG , which is located on chromosome 8q24, encodes a 660-kDa glycoprotein that supports the generation of thyroid hormones ( Xuan et al, 2019 ). A significant relationship between rs2069550 (case/control: 436/316, p = 0.01, OR = 1.49) of the TG gene and GD has been reported ( Gu et al, 2010 ).…”

“…In the Chinese Han population, rs2294025 (case/control: 9757/10626, p = 1.52 × 10 −9 , OR = 1.16) and rs7005834 (case/control: 9757/1062, p = 1.62 × 10 −7 , OR = 1.16) are two independent loci associated with susceptibility to GD ( Xuan et al, 2019 ). Also, the frequency of the TT genotype (case/control: 131/89, p = 0.0283, OR = 0.484) of rs2703013 was significantly lower in GD patients than in controls.…”