title: Robust evidence for five new Graves' disease risk loci from a staged genome-wide association analysis.
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.
authors.affiliation: State Key Laboratory of Medical Genomics, Ruijin Hospital Affiliated to Shanghai Jiaotong University SJTU School of Medicine, Shanghai 200025, China.
authors.forename: Shuang-Xia
authors.initials: SX
authors.lastname: Zhao
authors.forename: Li-Qiong
authors.initials: LQ
authors.lastname: Xue
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Zhao-Hui
authors.initials: ZH
authors.lastname: Gu
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Pan
authors.forename: Shao-Ying
authors.initials: SY
authors.lastname: Yang
authors.forename: Ming
authors.initials: M
authors.lastname: Zhan
authors.forename: Hai-Ning
authors.initials: HN
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Liang
authors.forename: Guan-Qi
authors.initials: GQ
authors.lastname: Gao
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Zhang
authors.forename: Guo-Yue
authors.initials: GY
authors.lastname: Yuan
authors.forename: Chang-Gui
authors.initials: CG
authors.lastname: Li
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Du
authors.forename: Bing-Li
authors.initials: BL
authors.lastname: Liu
authors.forename: Li-Bin
authors.initials: LB
authors.lastname: Liu
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
authors.forename: Qing
authors.initials: Q
authors.lastname: Su
authors.forename: Yong-De
authors.initials: YD
authors.lastname: Peng
authors.forename: Jia-Jun
authors.initials: JJ
authors.lastname: Zhao
authors.forename: Guang
authors.initials: G
authors.lastname: Ning
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Liming
authors.initials: L
authors.lastname: Liang
authors.forename: Lu
authors.initials: L
authors.lastname: Qi
authors.forename: Sai-Juan
authors.initials: SJ
authors.lastname: Chen
authors.forename: Zhu
authors.initials: Z
authors.lastname: Chen
authors.forename: Jia-Lun
authors.initials: JL
authors.lastname: Chen
authors.forename: Huai-Dong
authors.initials: HD
authors.lastname: Song
mesh_terms: D000017:ABO Blood-Group System / Q000235:genetics; D000328:Adult; D015703:Antigens, CD / Q000235:genetics; D001483:Base Sequence; D016022:Case-Control Studies; D003094:Collagen; D021901:DNA, Intergenic; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006111:Graves Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D022661:RNA, Untranslated / Q000235:genetics*; D011956:Receptors, Cell Surface / Q000235:genetics; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D000071176:Signaling Lymphocytic Activation Molecule Family; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D048069:Tumor Necrosis Factors / Q000235:genetics*
chemical_list: D000017:ABO Blood-Group System; D015703:Antigens, CD; C561455:C1qTNF6 protein, human; D021901:DNA, Intergenic; C581018:GPR174 protein, human; C485527:ITM2A protein, human; D008565:Membrane Proteins; D022661:RNA, Untranslated; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C000604060:SLAMF6 protein, human; D000071176:Signaling Lymphocytic Activation Molecule Family; D048069:Tumor Necrosis Factors; D000071177:Signaling Lymphocytic Activation Molecule Family Member 1; D003094:Collagen