A genome-wide association study identifies two new risk loci for Graves' disease
A genome-wide association study identifies two new risk loci for Graves' disease
复制标题
一项全基因组关联研究确定了格雷夫斯病的两个新风险位点
DOI：
10.1038/ng.898
复制
发表时间：
2011-09-01
期刊：
影响因子：
30.8
通讯作者：
Song, Huai-Dong
中科院分区：
文献类型：
--
作者：
Chu, Xun;Pan, Chun-Ming;Song, Huai-Dong
Graves病是一种常见的自身免疫性疾病，其特征是促甲状腺激素受体自身抗体（TRAb）和甲状腺功能亢进。为了研究Graves病的遗传结构，我们对1,536名Graves病患者（病例）和1,516名对照者进行了全基因组关联研究。我们进一步评估了第二组3，994例病例和3，510例对照中的一组相关SNP。我们确认了4个先前报道的基因座（在主要组织相容性复合体中，TSHR，CTLA 4和FCRL 3），并确定了2个新的易感基因座（在6 q27的RNASET 2-FGFR 1 OP-CCR 6区域（对于rs 9355610，P组合= 6.85 × 10− 10）和4p 14的基因间区域（对于rs6832151，P组合= 1.08 × 10− 13））。这些新关联的SNPs分别与6 q27处的RNASET 2、CHRNA 9和4p 14处先前未表征的基因的表达水平相关。此外，我们发现TSH和主要组织相容性复合物II类变异体与持续TRAb阳性Graves病密切相关。
Graves' disease is a common autoimmune disorder characterized by thyroid stimulating hormone receptor autoantibodies (TRAb) and hyperthyroidism. To investigate the genetic architecture of Graves' disease, we conducted a genome-wide association study in 1,536 individuals with Graves' disease (cases) and 1,516 controls. We further evaluated a group of associated SNPs in a second set of 3,994 cases and 3,510 controls. We confirmed four previously reported loci (in the major histocompatibility complex,TSHR,CTLA4andFCRL3) and identified two new susceptibility loci (theRNASET2-FGFR1OP-CCR6region at 6q27 (Pcombined= 6.85 × 10−10for rs9355610) and an intergenic region at 4p14 (Pcombined= 1.08 × 10−13for rs6832151)). These newly associated SNPs were correlated with the expression levels ofRNASET2at 6q27, ofCHRNA9and of a previously uncharacterized gene at 4p14, respectively. Moreover, we identified strong associations ofTSHRand major histocompatibility complex class II variants with persistently TRAb-positive Graves' disease.