A genome-wide association study in Han Chinese identifies a susceptibility locus for primary Sjogren's syndrome at 7q11.23
A genome-wide association study in Han Chinese identifies a susceptibility locus for primary Sjogren's syndrome at 7q11.23
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DOI：
10.1038/ng.2779
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发表时间：
2013-11-01
期刊：
影响因子：
30.8
通讯作者：
Zhang, Fengchun
中科院分区：
文献类型：
--
作者：
Li, Yongzhe;Zhang, Kunlin;Zhang, Fengchun
原发性干燥综合征是最常见的自身免疫性疾病之一。到目前为止，干燥综合征的遗传学研究主要依赖于候选基因方法。为了发现原发性干燥综合征新的遗传易感位点，我们在中国汉族人群中进行了三阶段全基因组关联研究。在发现阶段，我们分析了542例病例和1，050例对照的556，134个常染色体SNP。然后，我们在2个复制阶段验证了有希望的关联，包括1，303例病例和2，727例对照。联合分析确定7q11.23处的GTF 2 I（rs 117026326：P-组合= 1.31 x 10（-53），组合优势比（OR组合）= 2.20）为原发性干燥综合征的新易感位点。我们的分析也证实了先前报道的欧洲人在STAT 4，TNFAIP 3和主要组织相容性复合体（MHC）区域的相关性。对GTF 2 I周围区域的精细定位显示，GTF 2 I中的rs 117026326具有最显著的关联，相关SNP从GTF 2 I延伸到GTF 2 IRD 1-GTF 2 I。
Primary Sjogren's syndrome is one of the most common autoimmune diseases. So far, genetic studies of Sjogren's syndrome have relied mostly on candidate gene approaches. To identify new genetic susceptibility loci for primary Sjogren's syndrome, we performed a three-stage genome-wide association study in Han Chinese. In the discovery stage, we analyzed 556,134 autosomal SNPs in 542 cases and 1,050 controls. We then validated promising associations in 2 replication stages comprising 1,303 cases and 2,727 controls. The combined analysis identified GTF2I at 7q11.23 (rs117026326: P-combined = 1.31 x 10(-53), combined odds ratio (ORcombined) = 2.20) as a new susceptibility locus for primary Sjogren's syndrome. Our analysis also confirmed previously reported associations in Europeans in the regions of STAT4, TNFAIP3 and the major histocompatibility complex (MHC). Fine mapping of the region around GTF2I showed that rs117026326 in GTF2I had the most significant association, with associated SNPs extending from GTF2I to GTF2IRD1-GTF2I.