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Shuang-Xia Zhao, Li-Qiong Xue, Wei Liu, Zhao-Hui Gu, Chun-Ming Pan, Shao-Ying Yang, Ming Zhan, Hai-Ning Wang, Jun Liang, Guan-Qi Gao, Xiao-Mei Zhang, Guo-Yue Yuan, Chang-Gui Li, Wen-Hua Du, Bing-Li Liu, Li-Bin Liu, Gang Chen, Qing Su, Yong-De Peng, Jia-Jun Zhao, Guang Ning, Wei Huang, Liming Liang, Lu Qi, Sai-Juan Chen, Zhu Chen, Jia-Lun Chen, Huai-Dong Song, for The China Consortium for the Genetics of Autoimmune Thyroid Disease, Robust evidence for five new Graves' disease risk loci from a staged genome-wide association analysis, Human Molecular Genetics, Volume 22, Issue 16, 15 August 2013, Pages 3347–3362, https://doi.org/10.1093/hmg/ddt183
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Abstract
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.