title: Refined association of TSH receptor susceptibility locus to Graves' disease in the Chinese Han population.
abstract: BACKGROUND
  Convincing evidence has demonstrated the association of TSH receptor (TSHR) with Graves' disease (GD) in the Chinese Han population.
  
  
  OBJECTIVE
  The aim of this study was to identify the causal variants for GD in the region encompassing TSHR by a refining association study.
  
  
  METHODS
  GD patients (1536) and 1516 sex-matched controls were recruited in the first stage, and an additional 3832 GD patients and 3426 sex-matched controls were recruited in the replication stage. Genotyping was performed using Illumina Human660-Quad BeadChips or TaqMan single nucleotide polymorphism (SNP) Genotyping Assays and the Fluidigm EP1 platform.
  
  
  RESULTS
  When the results of regression analysis for 74 genotyped SNPs and 922 imputed SNPs in the first-stage cohort were combined, rs179243 and rs3783949 were the probable susceptibility SNPs associated with GD in TSHR. Eleven SNPs, including rs179243 and rs3783949, were selected to further refine the association in the replication study. Finally, rs12101261 and rs179243 were confirmed as independent GD susceptibility variants in the replication and combined populations. Further, we also found that the rate of persistent TSHR autoantibody positivity (pTRAb+) was significantly higher in the GD patients with the susceptible genotypes rs12101261 or rs179243 than in the GD patients carrying the protective genotypes, after the GD patients had been treated for more than 1 year.
  
  
  CONCLUSIONS
  These findings indicate that rs12101261 and rs179243 are the possible causal SNPs for GD susceptibility in the TSHR gene and could serve as genetic markers to predict the outcome of pTRAb+ in GD patients.
authors.affiliation: State Key Laboratory of Medical Genomics, Shanghai Institute of Endocrinology and Metabolism, Molecular Medicine Center, Ruijin Hospital Affiliated to Shanghai Jiaotong University (SJTU) School of Medicine, Shanghai 200025, China.
authors.forename: Bing-Li
authors.initials: BL
authors.lastname: Liu
authors.forename: Shao-Ying
authors.initials: SY
authors.lastname: Yang
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Li-Qiong
authors.initials: LQ
authors.lastname: Xue
authors.forename: Xia
authors.initials: X
authors.lastname: Chen
authors.forename: Chun-Ming
authors.initials: CM
authors.lastname: Pan
authors.forename: Zhao-Hui
authors.initials: ZH
authors.lastname: Gu
authors.forename: Ming
authors.initials: M
authors.lastname: Zhan
authors.forename: Xiao-Mei
authors.initials: XM
authors.lastname: Zhang
authors.forename: Jun
authors.initials: J
authors.lastname: Liang
authors.forename: Guan-Qi
authors.initials: GQ
authors.lastname: Gao
authors.forename: Wen-Hua
authors.initials: WH
authors.lastname: Du
authors.forename: Guo-Yue
authors.initials: GY
authors.lastname: Yuan
authors.forename: Ru
authors.initials: R
authors.lastname: Ying
authors.forename: Shuang-Xia
authors.initials: SX
authors.lastname: Zhao
authors.forename: Huai-Dong
authors.initials: HD
authors.lastname: Song
mesh_terms: D013956:Antithyroid Agents / Q000627:therapeutic use; D044466:Asian People; D016022:Case-Control Studies; D002681:China; D015331:Cohort Studies; D003131:Combined Modality Therapy; D004351:Drug Resistance; D005260:Female; D056726:Genetic Association Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D006111:Graves Disease / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D006801:Humans; D018828:Immunoglobulins, Thyroid-Stimulating / Q000032:analysis; D007457:Iodine Radioisotopes / Q000627:therapeutic use; D008297:Male; D020641:Polymorphism, Single Nucleotide; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D011989:Receptors, Thyrotropin / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D015203:Reproducibility of Results
chemical_list: D013956:Antithyroid Agents; D018828:Immunoglobulins, Thyroid-Stimulating; D007457:Iodine Radioisotopes; D019275:Radiopharmaceuticals; D011989:Receptors, Thyrotropin; C094372:thyrotropin-binding inhibitory immunoglobulin