Abstract

We performed a genome-wide association study (GWAS) of systemic lupus erythematosus (SLE) in a Chinese Han population by genotyping 1,047 cases and 1,205 controls using Illumina Human610-Quad BeadChips and replicating 78 SNPs in two additional cohorts (3,152 cases and 7,050 controls). We identified nine new susceptibility loci (ETS1, IKZF1, RASGRP3, SLC15A4, TNIP1, 7q11.23, 10q11.22, 11q23.3 and 16p11.2; 1.77 × 10−25Pcombined ≤ 2.77 × 10−8) and confirmed seven previously reported loci (BLK, IRF5, STAT4, TNFAIP3, TNFSF4, 6q21 and 22q11.21; 5.17 × 10−42Pcombined ≤ 5.18 × 10−12). Comparison with previous GWAS findings highlighted the genetic heterogeneity of SLE susceptibility between Chinese Han and European populations. This study not only advances our understanding of the genetic basis of SLE but also highlights the value of performing GWAS in diverse ancestral populations.

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Change history

  • Corrected online 04 December 2009

    In the version of this article initially published, there were two errors in the author affiliations and corresponding author details. Jian-Jun Liu is also affiliated with footnote 17, and Sen Yang and Xue-Jun Zhang are the corresponding authors. These errors have been corrected in the HTML and PDF versions of the article.

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Acknowledgements

We thank all study participants. This study was funded by the National Natural Science Foundation (30972727), the Key Project of National Natural Science Foundation (30530670 and 30830089), the Anhui Provincial Special Scientific Program (2007-7) and the Anhui Skin Genetic Study Innovative Research Team Program (TD200701).

Author information

Author notes

    • Jian-Wen Han
    • , Hou-Feng Zheng
    •  & Yong Cui

    These authors contributed equally to this work.

Affiliations

  1. Institute of Dermatology and Department of Dermatology at NO. 1 Hospital, Anhui Medical University, Hefei, Anhui, China.

    • Jian-Wen Han
    • , Hou-Feng Zheng
    • , Yong Cui
    • , Liang-Dan Sun
    • , Dong-Qing Ye
    • , Zhi Hu
    • , Xian-Bo Zuo
    • , Fu-Sheng Zhou
    • , Wen-Hui Du
    • , Yi-Lin Cheng
    • , Jian-Qiang Yang
    • , Song-Ke Shen
    • , Jian Li
    • , Yu-Jun Sheng
    • , Min Gao
    • , Feng-Li Xiao
    • , Cheng Quan
    • , Chi Zhang
    • , Zheng Zhang
    • , Kun-Ju Zhu
    • , Yang Li
    • , Da-Yan Hu
    • , Wen-Sheng Lu
    • , Sheng-Xiu Liu
    • , Hui Li
    • , Yun-Qing Ren
    • , Zai-Xing Wang
    • , Chun-Jun Yang
    • , Pei-Guang Wang
    • , Wen-Ming Zhou
    • , Yong-Mei Lv
    • , An-Ping Zhang
    • , Sheng-Quan Zhang
    • , Da Lin
    • , Feng-Yu Zhang
    • , Sen Yang
    • , Jian-Jun Liu
    •  & Xue-Jun Zhang
  2. Key Laboratory of Dermatology, Anhui Medical University, Ministry of Education, China, Hefei, Anhui, China.

    • Jian-Wen Han
    • , Hou-Feng Zheng
    • , Yong Cui
    • , Liang-Dan Sun
    • , Dong-Qing Ye
    • , Zhi Hu
    • , Xian-Bo Zuo
    • , Fu-Sheng Zhou
    • , Wen-Hui Du
    • , Yi-Lin Cheng
    • , Jian-Qiang Yang
    • , Song-Ke Shen
    • , Jian Li
    • , Yu-Jun Sheng
    • , Min Gao
    • , Feng-Li Xiao
    • , Cheng Quan
    • , Chi Zhang
    • , Zheng Zhang
    • , Kun-Ju Zhu
    • , Yang Li
    • , Da-Yan Hu
    • , Wen-Sheng Lu
    • , Sheng-Xiu Liu
    • , Hui Li
    • , Yun-Qing Ren
    • , Zai-Xing Wang
    • , Chun-Jun Yang
    • , Pei-Guang Wang
    • , Wen-Ming Zhou
    • , Yong-Mei Lv
    • , An-Ping Zhang
    • , Sheng-Quan Zhang
    • , Da Lin
    • , Feng-Yu Zhang
    • , Sen Yang
    • , Jian-Jun Liu
    •  & Xue-Jun Zhang
  3. Department of Dermatology, Huashan Hospital of Fudan University, Shanghai, China.

    • Jin-Hua Xu
    •  & Xue-Jun Zhang
  4. Department of Rheumatology, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China.

    • Zhi-Ming Cai
    •  & Qing-Wen Wang
  5. Chinese National Human Genome Center at Shanghai, Shanghai, China.

    • Wei Huang
    • , Guo-Ping Zhao
    • , Min Shen
    •  & Ying Wang
  6. Department of Dermatology, Xiangya Hospital, Central South University, Changsha, Hunan, China.

    • Hong-Fu Xie
    •  & Xiao-Xia Zuo
  7. Department of Dermatology, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

    • Hong Fang
    •  & Wei-Fang Zhu
  8. Department of Dermatology, Epigenetic Research Center, Second Xiangya Hospital, Central South University, Changsha, Hunan, China.

    • Qian-Jin Lu
    •  & Fei Gao
  9. Department of Rheumatology at NO. 1 Hospital, Anhui Medical University, Hefei, Anhui, China.

    • Jian-Hua Xu
  10. Department of Rheumatology, Affiliated Provincial Hospital of Anhui Medical University, Hefei, Anhui, China.

    • Xiang-Pei Li
  11. Department of Rheumatology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.

    • Yun-Feng Pan
    •  & Jian-Lin Huang
  12. Department of Dermatology, The Second Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, China.

    • Dan-Qi Deng
    •  & Pei-Lian Zhang
  13. Department of Dermatology, The Second Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.

    • Fan-Qin Zeng
    •  & Qing Guo
  14. Department of Rheumatology, Shenzhen Fourth People's Hospital, Shenzhen, Guangdong, China.

    • Zhi-Zhong Ye
    •  & Bo Li
  15. Department of Dermatology, China-Japan Friendship Hospital, Beijing, China.

    • Xiao-Yan Zhang
    •  & Li Ma
  16. Department of Dermatology, Southwest Hospital, Third Military Medical University, Chongqing, China.

    • Fei Hao
    •  & Zhi-Fang Zhai
  17. Human Genetics, Genome Institute of Singapore, Singapore, Singapore.

    • Yi Li
    • , Hui Qi Low
    •  & Jian-Jun Liu

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Contributions

X.-J.Z. conceived of this study and obtained financial support. X.-J.Z., J.-J.L. and S.Y. designed the study. J.-W.H., H.-F.Z., Y.C. and L.-D.S. participated in the design and were responsible for sample selection, genotyping and project management. D.-Q.Y., Z.H., Jin-Hua Xu, Z.-M.C., H.-F.X., H.F., Q.-J.L., Jian-Hua Xu, X.-P.L., Y.-F.P., D.-Q.D., F.-Q.Z., Z.-Z.Y., X.-Y.Z., Q.-W.W., F.H., L.M., X.-X.Z., W.-F.Z., F.G., P.-L.Z., Q.G., B.L., M.G., F.-L.X., J.-L.H., S.-X.L., H.L., Z.-X.W., C.-J.Y., P.-G.W., W.-M.Z., A.-P.Z., D.L. and Z.-F.Z. conducted sample selection and data management. W.-H.D., J.-Q.Y., S.-K.S., J.L., Y.-J.S., K.-J.Z., Yang Li, D.-Y.H. and Y.-M.L. undertook recruitment, collected phenotype data, undertook related data handling and calculation, managed recruitment and obtained biological samples. W.H., G.-P.Z., F.-S.Z., Y.-L.C., C.Q., C.Z., Z.Z., W.-S.L., Y.-Q.R., S.-Q.Z., M.S. and Y.W. performed genotyping analysis. H.-F.Z., X.-B.Z., Yi Li, H.Q.L. and F.-Y.Z. undertook data processing, statistical analysis and bioinformatics investigations. All the authors contributed to the final paper, with X.-J.Z., J.-J.L., S.Y., J.-W.H., H.-F.Z., Y.C. and L.-D.S playing key roles.

Corresponding authors

Correspondence to Sen Yang or Xue-Jun Zhang.

Supplementary information

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  1. 1.

    Supplementary Text and Figures

    Supplementary figures 1–4 and Supplementary Tables 1–4