Robust evidence for five new Graves disease risk loci from a staged genome-wide association analysis
Robust evidence for five new Graves disease risk loci from a staged genome-wide association analysis
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五个新坟墓的有力证据
DOI：
10.1093/hmg/ddt183
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发表时间：
2013-08-15
影响因子：
3.5
通讯作者：
Song, Huai-Dong
中科院分区：
文献类型：
--
作者：
Zhao, Shuang-Xia;Xue, Li-Qiong;Song, Huai-Dong
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引发的。然而，在不同种族中仅确认了少数 GD 风险基因座，并且必须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 名对照组进行了一项三阶段研究，以确定新的 GD 风险位点，并发现整个人群中五个新易感位点存在全基因组显着关联：Xq21.1 处的 GPR174-ITM2A、22q12.313.1 处的 C1QTNF6-RAC2、1q23.2 处的 SLAMF6、ABO 9q34.2 处有一个基因间区域，14q32.2 处有两个非编码 RNA，8q24.22 处有一个先前的不定基因座 TG（P 组合 5 10(8)）。 14q32.2和8q24.22相应变体的基因型分别与C14orf64和跳过外显子46的TG转录本的表达水平相关。这项研究增加了 GD 基因座的数量，并提供了令人信服的证据，表明非编码 RNA 可能参与 GD 的发病机制。
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 22q12.313.1, 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 (P-combined 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.