A genome-wide association study in Han Chinese identifies a susceptibility locus for primary Sjögren's syndrome at 7q11.23

• Published in: Nature genetics Vol. 45; no. 11; pp. 1361 - 1365
• Main Authors: Li, Yongzhe, Zhang, Kunlin, Chen, Hua, Sun, Fei, Xu, Juanjuan, Wu, Ziyan, Li, Ping, Zhang, Liuyan, Du, Yang, Luan, Haixia, Li, Xi, Wu, Lijun, Li, Hongbin, Wu, Huaxiang, Li, Xiangpei, Li, Xiaomei, Zhang, Xiao, Gong, Lu, Dai, Lie, Sun, Lingyun, Zuo, Xiaoxia, Xu, Jianhua, Gong, Huiping, Li, Zhijun, Tong, Shengquan, Wu, Min, Li, Xiaofeng, Xiao, Weiguo, Wang, Guochun, Zhu, Ping, Shen, Min, Liu, Shengyun, Zhao, Dongbao, Liu, Wei, Wang, Yi, Huang, Cibo, Jiang, Quan, Liu, Guijian, Liu, Bin, Hu, Shaoxian, Zhang, Wen, Zhang, Zhuoli, You, Xin, Li, Mengtao, Hao, Weixin, Zhao, Cheng, Leng, Xiaomei, Bi, Liqi, Wang, Yongfu, Zhang, Fengxiao, Shi, Qun, Qi, Wencheng, Zhang, Xuewu, Jia, Yuan, Su, Jinmei, Li, Qin, Hou, Yong, Wu, Qingjun, Xu, Dong, Zheng, Wenjie, Zhang, Miaojia, Wang, Qian, Fei, Yunyun, Zhang, Xuan, Li, Jing, Jiang, Ying, Tian, Xinping, Zhao, Lidan, Wang, Li, Zhou, Bin, Li, Yang, Zhao, Yan, Zeng, Xiaofeng, Ott, Jurg, Wang, Jing, Zhang, Fengchun
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.11.2013; Nature Publishing Group
• Subjects: 45/43; 631/208/205/2138; 692/699/249/1313; Agriculture; Animal Genetics and Genomics; Autoimmune diseases; Biomedicine; Cancer Research; China; Chromosome mapping; Chromosomes, Human, Pair 7 - genetics; Confidence intervals; Disease; DNA-Binding Proteins - genetics; Gene expression; Gene Function; Genetic aspects; Genetic Predisposition to Disease; Genetic susceptibility; Genome-Wide Association Study; Genomes; Human Genetics; Humans; Identification and classification; Intracellular Signaling Peptides and Proteins - genetics; letter; Logistics; Major Histocompatibility Complex - genetics; Methods; Nuclear Proteins - genetics; Pathogenesis; Polymorphism, Single Nucleotide; Quality control; Single nucleotide polymorphisms; Sjogren's syndrome; Sjogren's Syndrome - genetics; STAT4 Transcription Factor - genetics; Testing; Transcription Factors, TFII - genetics; Tumor Necrosis Factor alpha-Induced Protein 3; China
• ISSN: 1061-4036; 1546-1718; 1546-1718
• DOI: 10.1038/ng.2779

Jing Wang, Fengchun Zhang and colleagues report the results of a genome-wide association study of primary Sjögren's syndrome, a common autoimmune disease. They confirm associations in the STAT4 , TNFAIP3 and HLA regions and identify a new susceptibility locus in the GTF2I region at 7q11.23. Primary Sjögren's syndrome is one of the most common autoimmune diseases. So far, genetic studies of Sjögren's syndrome have relied mostly on candidate gene approaches. To identify new genetic susceptibility loci for primary Sjögren'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 × 10 −53 , combined odds ratio (OR combined ) = 2.20) as a new susceptibility locus for primary Sjögren'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 .