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A genome-wide association study in Han Chinese identifies multiple susceptibility loci for IgA nephropathy

Nature Genetics volume 44, pages 178–182 (2012)Cite this article

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Abstract

We performed a two-stage genome-wide association study of IgA nephropathy (IgAN) in Han Chinese, with 1,434 affected individuals (cases) and 4,270 controls in the discovery phase and follow-up of the top 61 SNPs in an additional 2,703 cases and 3,464 controls. We identified associations at 17p13 (rs3803800, P = 9.40 × 10−11, OR = 1.21; rs4227, P = 4.31 × 10−10, OR = 1.23) and 8p23 (rs2738048, P = 3.18 × 10−14, OR = 0.79) that implicated the genes encoding tumor necrosis factor (TNFSF13) and α-defensin (DEFA) as susceptibility genes. In addition, we found multiple associations in the major histocompatibility complex (MHC) region (rs660895, P = 4.13 × 10−20, OR = 1.34; rs1794275, P = 3.43 × 10−13, OR = 1.30; rs2523946, P = 1.74 × 10−11, OR = 1.21) and confirmed a previously reported association at 22q12 (rs12537, P = 1.17 × 10−11, OR = 0.78). We also found that rs660895 was associated with clinical subtypes of IgAN (P = 0.003), proteinuria (P = 0.025) and IgA levels (P = 0.047). Our findings show that IgAN is associated with variants near genes involved in innate immunity and inflammation.

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Figure 1: Manhattan plots of the P values of association obtained by analysis of the 444,882 polymorphic SNPs in the discovery sample of 1,434 IgAN cases and 4,270 controls.
Figure 2: Regional plots of the association results from the discovery sample and recombination rates within the two new susceptibility loci.

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Acknowledgements

We are grateful to all the subjects and healthy volunteers who participated in this work. We thank the staff in The First Affiliated Hospital of Sun Yat-sen University for help with sample collection, DNA extraction and sample storage; W.Y. Meah, X. Chen, H.B. Toh, C.H. Wong, P.L. Ng and I.D. Irwan for performing the genotyping; Z.X. Zhang and Z. B. Hu for providing the control samples in the validation study and R. Johnson for reviewing the manuscript and providing constructive suggestions. This work was funded by the Major State Basic Research Development Program of China (973 program) (2012CB517700-2012CB517706), Key Program of National Natural Science Foundation of China (81130012), National Natural Science Foundation of China for Distinguished Young Scholars (30925019) and the Agency for Science & Technology and Research of Singapore (A*STAR) (to J.-J.L.).

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Author notes

  1. Xue-Qing Yu, Ming Li and Hong Zhang: These authors contributed equally to the work.

Authors and Affiliations

  1. Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China

    Xue-Qing Yu, Ming Li, Xin Wei, Wei Wang, Zhi-Jian Li, Xue-Qing Tang & Li Fan

  2. Key Laboratory of Nephrology, Ministry of Health, Guangzhou, Guangdong, China

    Xue-Qing Yu, Ming Li, Xin Wei, Wei Wang, Zhi-Jian Li, Xue-Qing Tang & Li Fan

  3. Renal Division, Peking University First Hospital, Peking University, Institute of Nephrology, Beijing, China

    Hong Zhang & Li Zhu

  4. Human Genetics, Genome Institute of Singapore, Singapore

    Hui-Qi Low, Kar-Seng Sim, Yi Li, Jia-Nee Foo & Jian-Jun Liu

  5. Department of Nephrology, Nanjing General Hospital of Nanjing Military Command, Nanjing, Jiangsu, China

    Jin-Quan Wang & Zhi-Hong Liu

  6. Institute of Dermatology and Department of Dermatology, No.1 Hospital, Anhui Medical University, Hefei, Anhui, China

    Liang-Dan Sun, Xian-Yong Yin & Xue-Jun Zhang

  7. State Key Laboratory Incubation Base of Dermatology, Ministry of National Science and Technology, Hefei, Anhui, China

    Liang-Dan Sun, Xian-Yong Yin & Xue-Jun Zhang

  8. Department of Nephrology, Fuzhou General Hospital of Nanjing Military Command, Fuzhou, Fujian, China

    Jian Chen

  9. Department of Nephrology, The Second Hospital of Shanxi Medical University, Taiyuan, Shanxi, China

    Rong-Shan Li

  10. Department of Nephrology, The First Affiliated Hospital of Fujian Medical University, Fuzhou, Fujian, China

    Jian-Xin Wan

  11. Department of Nephrology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China

    Zhang-Suo Liu

  12. Department of Nephrology, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China

    Tan-Qi Lou

  13. Department of Hematology, Peking University People's Hospital, Beijing, China

    Xiao-Jun Huang

  14. School of Life Sciences, Anhui Medical University, Hefei, Anhui, China

    Jian-Jun Liu

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Contributions

H.Z., Z.-H.L., M.L., X.W., J.-Q.W., J.C., R.-S.L., J.-X.W., Z.-S.L., L.Z., T.-Q.L. and X.-J.H. performed clinical characterization and recruitment of subjects and contributed samples; X.W., X.-Q.T., Z.-J.L., L.F. and W.W. prepared DNA; M.L. and X.-Y.Y. performed experiments. J.-J.L., H.-Q.L., K.-S.S. and M.L. analyzed data; Y.L., J.-N.F. and L.-D.S. contributed to analytical support and discussion; X.-Q.Y. and X.-J.Z. provided the platform and organized the study; J.-J.L., X.-Q.Y. and M.L. prepared the manuscript; J.-J.L. and X.-Q.Y. conceived and supervised the project.

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Correspondence to Xue-Qing Yu or Jian-Jun Liu.

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Yu, XQ., Li, M., Zhang, H. et al. A genome-wide association study in Han Chinese identifies multiple susceptibility loci for IgA nephropathy. Nat Genet 44, 178–182 (2012). https://doi.org/10.1038/ng.1047

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