Robustevidence for fivenewgraves'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 identifynewrisk loci forGDandfoundgenome-wide significantassociations in the overall populations forfive novel susceptibility loci: the GPR174-ITM2Aat Xq21.1,C1QTNF6-RAC2 at 22q12.3-13.1,SLAMF 6 at 1q23.2,ABO at 9q34.2 and an intergenic region harboring two non-coding RNA sat 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 ofGDloci with compelling evidence and indicated that non-coding RNAs might be potentially involved in the pathogenesis of GD. © The Author 2013. Published by Oxford University Press. All rights reserved.