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

Abstract

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: Pcombined = 1.31 × 10−53, combined odds ratio (ORcombined) = 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.

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Figure 1: Regional plot of association results for the newly identified primary Sjögren's syndrome susceptibility locus at 7q11.23.

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Acknowledgements

We thank all participants recruited in this study. This work was supported by grants from the Research Special Fund for Public Welfare Industry of Health (201202004 to Fengchun Zhang), the National Science Technology Pillar Program in the 11th Five-Year Plan (2008BAI59B03 to Fengchun Zhang), the National Program on Key Research Project of New Drug Innovation (2012ZX09303006-002 to Fengchun Zhang), the Knowledge Innovation Program of the Chinese Academy of Sciences (KSCX2-EW-J-8 to J.W.), the CAS/SAFEA International Partnership Program for Creative Research Teams (Y2CX131003 to J.W.) and the National Natural Science Foundation of China (81072486 and 81172857 to Yongzhe Li and 81101545 to K.Z.).

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Fengchun Zhang and J.W. conceived and designed the overall project. Yongzhe Li and H.C. directed and managed sample collection and diagnosis. K.Z. supervised data analysis. Yongzhe Li, K.Z., H.C., F.S., Juanjuan Xu and Z.W. managed clinical information and genotyping. K.Z., L. Zhang, Y.D. and J.O. performed statistical data analysis. K.Z. and J.W. wrote the manuscript. J.O., L. Zhang, Yongzhe Li, H.C. and Fengchun Zhang revised the manuscript. The following authors contributed to sample collection: F.S., Juanjuan Xu, Z.W., P.L., H. Luan, Xi Li, L. Wu, H. Li, H.W., Xiangpei Li, Xiaomei Li, Xiao Zhang, L.G., L.D., L.S., X. Zuo, Jianhua Xu, H.G., Z.L., S.T., M.W., Xiaofeng Li, W.X., G.W., P.Z., M.S., S.L., D.Z., W.L., Yi Wang, C.H., Q.J., G.L., B.L., S.H., W. Zhang, Z.Z., X.Y., M.L., W.H., C.Z., X. Leng, L.B., Yongfu Wang, Fengxiao Zhang, Q.S., W.Q., Xuewu Zhang, Y. Jia, J.S., Q.L., Y.H., Q. Wu, D.X., W. Zheng, M.Z., Q. Wang, Y.F., Xuan Zhang, J.L., Y. Jiang, X.T., L. Zhao, L. Wang, B.Z., Yang Li, Y.Z. and X. Zeng. Fengchun Zhang, J.W., Yongzhe Li and K.Z. obtained funding for this study. All authors reviewed the manuscript.

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Correspondence to Jing Wang or Fengchun Zhang.

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Li, Y., Zhang, K., Chen, H. et al. A genome-wide association study in Han Chinese identifies a susceptibility locus for primary Sjögren's syndrome at 7q11.23. Nat Genet 45, 1361–1365 (2013). https://doi.org/10.1038/ng.2779

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