Robust evidence for five new Graves' disease risk loci from a staged genome-wide association analysis

Hum Mol Genet. 2013 Aug 15;22(16):3347-62. doi: 10.1093/hmg/ddt183. Epub 2013 Apr 23.

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.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ABO Blood-Group System / genetics
  • Adult
  • Antigens, CD / genetics
  • Base Sequence
  • Case-Control Studies
  • Collagen
  • DNA, Intergenic
  • Female
  • Genetic Loci
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Genotype
  • Graves Disease / genetics*
  • Humans
  • Male
  • Membrane Proteins / genetics
  • Middle Aged
  • Molecular Sequence Data
  • Polymorphism, Single Nucleotide
  • RNA, Untranslated / genetics*
  • Receptors, Cell Surface / genetics
  • Receptors, G-Protein-Coupled / genetics
  • Signaling Lymphocytic Activation Molecule Family
  • Signaling Lymphocytic Activation Molecule Family Member 1
  • Tumor Necrosis Factors / genetics*

Substances

  • ABO Blood-Group System
  • Antigens, CD
  • C1qTNF6 protein, human
  • DNA, Intergenic
  • GPR174 protein, human
  • ITM2A protein, human
  • Membrane Proteins
  • RNA, Untranslated
  • Receptors, Cell Surface
  • Receptors, G-Protein-Coupled
  • SLAMF6 protein, human
  • Signaling Lymphocytic Activation Molecule Family
  • Tumor Necrosis Factors
  • Signaling Lymphocytic Activation Molecule Family Member 1
  • Collagen

Associated data

  • GENBANK/JX073282
  • GENBANK/JX073283