State Key Laboratory of Medical Genomics, Ruijin Hospital Affiliated to Shanghai Jiaotong University SJTU School of Medicine, Shanghai 200025, China.
Hum Mol Genet. 2013 Aug 15;22(16):3347-62. doi: 10.1093/hmg/ddt183. Epub 2013 Apr 23.
Graves' disease (GD), characterized by autoantibodies targeting antigens specifically expressed in thyroid tissues causing hyperthyroidism, is triggered by a combination of genetic and environmental factors. However, only a few loci for GD risk were confirmed in the various ethnic groups, and additional genetic determinants have to be detected. In this study, we carried out a three-stage study in 9529 patients with GD and 9984 controls to identify new risk loci for GD and found genome-wide significant associations in the overall populations for five novel susceptibility loci: the GPR174-ITM2A at Xq21.1, C1QTNF6-RAC2 at 22q12.3-13.1, SLAMF6 at 1q23.2, ABO at 9q34.2 and an intergenic region harboring two non-coding RNAs at 14q32.2 and one previous indefinite locus, TG at 8q24.22 (Pcombined < 5 × 10(-8)). The genotypes of corresponding variants at 14q32.2 and 8q24.22 were correlated with the expression levels of C14orf64 and a TG transcript skipping exon 46, respectively. This study increased the number of GD loci with compelling evidence and indicated that non-coding RNAs might be potentially involved in the pathogenesis of GD.
格雷夫斯病（GD）的特征是针对甲状腺组织中特异性表达的抗原的自身抗体导致甲状腺功能亢进，是由遗传和环境因素共同作用引发的。然而，在不同种族群体中，只有少数 GD 风险基因座被证实，还需要检测其他遗传决定因素。在这项研究中，我们对 9529 名 GD 患者和 9984 名对照进行了三阶段研究，以确定 GD 的新风险基因座，并在总体人群中发现了五个新的易感基因座的全基因组显著关联：Xq21.1 上的 GPR174-ITM2A、22q12.3-13.1 上的 C1QTNF6-RAC2、1q23.2 上的 SLAMF6、9q34.2 上的 ABO 和包含两个非编码 RNA 的 14q32.2 上的基因间区域以及一个以前不确定的基因座 8q24.22（Pcombined < 5 × 10(-8)）。14q32.2 和 8q24.22 相应变异型的基因型与 C14orf64 和一个 TG 转录本跳过外显子 46 的表达水平相关。这项研究增加了 GD 基因座数量，提供了有力证据，并表明非编码 RNA 可能参与 GD 的发病机制。
