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Psoriasis genome-wide association study identifies susceptibility variants within LCE gene cluster at 1q21

Nature Genetics 41, 205–210 (2009) | Download Citation

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Abstract

We report the first large genome-wide association study (GWAS) in a Chinese population to identify susceptibility variants for psoriasis using a two-stage case-control design. In the first stage, we carried out a genome-wide association analysis in 1,139 cases and 1,132 controls of Chinese Han ancestry using Illumina Human 610-Quad BeadChips. In the second stage, we took top SNPs forward for replication in two independent samples of 5,182 cases and 6,516 controls of Chinese Han ancestry, and 539 cases and 824 controls of Chinese Uygur ancestry. In addition to the strong replication for two known susceptibility loci MHC (rs1265181, P = 1.93 × 10−208, OR = 22.62) and IL12B (rs3213094, Pcombined = 2.58 × 10−26, OR = 0.78), we identified a new susceptibility locus within the LCE gene cluster on 1q21 (rs4085613, Pcombined = 6.69 × 10−30, OR = 0.76).

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Acknowledgements

We thank G.P. Zhao, G.Y. Xu, L. Jin, X. Zhang, S.J. Xu and Z.G. Lin for assistance. And we would like to thank all the volunteers who took part in this work. We also want to thank L. Yi and E. Tantoso for their assistance in data analysis. This work was funded by the Anhui Provincial Special Scientific Program (2007-7), the High-Tech Research and Development Program of China (863 Plan) (2007AA02Z161), the Key Project of Natural Science Foundation of China (30530670), National Basic Research Program of China (973 Plan) (2007B516801), General Program of National Natural Science Foundation of China (30671895, 30771196, 30771942) and Agency for Science & Technology and Research of Singapore (A*STAR) (for J.J.L. and X.Y.L.).

Author information

Affiliations

  1. Institute of Dermatology and Department of Dermatology at No.1 Hospital, Anhui Medical University, Hefei, Anhui 230022, China.

    • Xue-Jun Zhang
    • , Sen Yang
    • , Liang-Dan Sun
    • , Feng-Yu Zhang
    • , Qi-Xing Zhu
    • , Chi Zhang
    • , Wen-Hui Du
    • , Hui Li
    • , Feng-Li Xiao
    • , Zai-Xing Wang
    • , Yong Cui
    • , Hui Cheng
    • , Hou-Feng Zheng
    • , Shu-Mei Zhang
    • , Hong-Yan Wang
    • , Yi-Lin Cheng
    • , Jian-Wen Han
    • , Cheng Quan
    • , Bin Chen
    • , Jun-Lin Liu
    • , Da Lin
    • , Li Fan
    • , An-Ping Zhang
    • , Sheng-Xiu Liu
    • , Chun-Jun Yang
    • , Pei-Guang Wang
    • , Wen-Ming Zhou
    • , Guo-Shu Lin
    • , Xing Fan
    • , Min Gao
    • , Wen-Sheng Lu
    • , Zheng Zhang
    • , Kun-Ju Zhu
    • , Song-Ke Shen
    • , Min Li
    • , Xiao-Yan Zhang
    • , Ting-Ting Cao
    • , Wei Ren
    • , Xin Zhang
    • , Jun He
    • , Xian-Fa Tang
    • , Shun Lu
    • , Jian-Qiang Yang
    • , Lin Zhang
    • , Dan-Ni Wang
    • , Feng Yuan
    • , Xian-Yong Yin
    •  & Jian-Jun Liu

  2. The Key Laboratory of Gene Resource Utilization for Severe Diseases, Ministry of Education and Anhui Province, Hefei, Anhui 230032, China.

    • Xue-Jun Zhang
    • , Sen Yang
    • , Liang-Dan Sun
    • , Feng-Yu Zhang
    • , Qi-Xing Zhu
    • , Chi Zhang
    • , Wen-Hui Du
    • , Hui Li
    • , Feng-Li Xiao
    • , Zai-Xing Wang
    • , Yong Cui
    • , Hui Cheng
    • , Hou-Feng Zheng
    • , Shu-Mei Zhang
    • , Hong-Yan Wang
    • , Yi-Lin Cheng
    • , Qiao-Yun Fang
    • , Fu-Sheng Zhou
    • , Jian-Wen Han
    • , Cheng Quan
    • , Bin Chen
    • , Jun-Lin Liu
    • , Da Lin
    • , Li Fan
    • , An-Ping Zhang
    • , Sheng-Xiu Liu
    • , Chun-Jun Yang
    • , Pei-Guang Wang
    • , Wen-Ming Zhou
    • , Guo-Shu Lin
    • , Xing Fan
    • , Min Gao
    • , Wen-Sheng Lu
    • , Zheng Zhang
    • , Kun-Ju Zhu
    • , Song-Ke Shen
    • , Min Li
    • , Xiao-Yan Zhang
    • , Ting-Ting Cao
    • , Wei Ren
    • , Xin Zhang
    • , Jun He
    • , Xian-Fa Tang
    • , Shun Lu
    • , Jian-Qiang Yang
    • , Lin Zhang
    • , Dan-Ni Wang
    • , Feng Yuan
    • , Xian-Yong Yin
    •  & Jian-Jun Liu

  3. Department of Dermatology and Venereology, Anhui Medical University, Hefei, Anhui 230032, China.

    • Xue-Jun Zhang
    • , Sen Yang
    • , Liang-Dan Sun
    • , Feng-Yu Zhang
    • , Qi-Xing Zhu
    • , Fu-Ren Zhang
    • , Chi Zhang
    • , Wen-Hui Du
    • , Xiong-Ming Pu
    • , Hui Li
    • , Feng-Li Xiao
    • , Zai-Xing Wang
    • , Yong Cui
    • , Xue-Qin Yang
    • , Hui Cheng
    • , Hou-Feng Zheng
    • , Shu-Mei Zhang
    • , Hong-Yan Wang
    • , Yi-Lin Cheng
    • , Jian-Wen Han
    • , Cheng Quan
    • , Bin Chen
    • , Jun-Lin Liu
    • , Da Lin
    • , Li Fan
    • , An-Ping Zhang
    • , Sheng-Xiu Liu
    • , Chun-Jun Yang
    • , Pei-Guang Wang
    • , Wen-Ming Zhou
    • , Guo-Shu Lin
    • , Wei-Dong Wu
    • , Xing Fan
    • , Min Gao
    • , Bao-Qi Yang
    • , Wen-Sheng Lu
    • , Zheng Zhang
    • , Kun-Ju Zhu
    • , Song-Ke Shen
    • , Min Li
    • , Xiao-Yan Zhang
    • , Ting-Ting Cao
    • , Wei Ren
    • , Xin Zhang
    • , Jun He
    • , Xian-Fa Tang
    • , Shun Lu
    • , Jian-Qiang Yang
    • , Lin Zhang
    • , Dan-Ni Wang
    • , Feng Yuan
    •  & Xian-Yong Yin

  4. Chinese National Human Genome Center at Shanghai, Shanghai 201203, China.

    • Wei Huang
    • , Hong-Jie Huang
    •  & Hai-Feng Wang

  5. The National Engineering Center for Biochip Design and Engineer in Shanghai, Shanghai 201203, China.

    • Wei Huang
    • , Hong-Jie Huang
    •  & Hai-Feng Wang

  6. Shandong Provincial Institute of Dermatology and Venereology, Jinan, Shandong 250022, China.

    • Fu-Ren Zhang
    •  & Bao-Qi Yang

  7. Department of Dermatology, People's Hospital of Xinjiang Uygur Autonomous Region, Urumchi, Xinjiang 830001, China.

    • Xiong-Ming Pu
    •  & Wei-Dong Wu

  8. Department of Dermatology, Southwest Hospital, Third Military Medical University, Chongqing, 400038, China.

    • Fei Hao

  9. Department of Dermatology, Ruijin Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai 200025, China.

    • Jie Zheng

  10. Department of Dermatology, The General Hospital of Air Force, PLA, Beijing 100036, China.

    • Xue-Qin Yang

  11. Department of Dermatology, No. 1 Hospital of China Medical University, Shenyang, Liaoning 110001, China.

    • Chun-Di He

  12. Department of Dermatology, the 1st Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116011, China.

    • Xiao-Ming Liu

  13. Department of Dermatology, Changzheng Hospital, Tianjin 300120, China.

    • Li-Min Xu

  14. Department of Dermatology, Peking University People's Hospital, Beijing 100044, China.

    • Jian-Zhong Zhang

  15. Department of Dermatology, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui 241000, China.

    • Bi-Hua Ji

  16. Department of Dermatology, Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, China.

    • Yu-Zhen Li

  17. Human Genetics, Genome Institute of Singapore, Singapore 138672, Singapore.

    • Xin-Yi Lin
    •  & Jian-Jun Liu

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Contributions

X.-J.Z. conceived of this study and obtained financial support. X.-J.Z., S.Y. and J.-J.L. designed it. S.Y., Q.-X.Z., F.-L.X., Y.C., W.-H.D., H.L., S.-M.Z., H.C., Z.-X.W., D.L., L.F., A.-P.Z., H.-Y.W., S.-X.L., C.-J.Y., P.-G.W., W.-M.Z., G.-S.L. and X.F. conducted sample selection and data management. W.-S.L., Z.Z., K.-J.Z., J.-L.L., S.-K.S., M.L., X.-Y.Z., T.-T.C., W.R., X.Z., J.H., X.-F.T., S.L., J.-Q.Y., L.Z., D.-N.W., F.Y., M.G. and X.-Y.Y. coordinated and/or undertook recruitment, collected phenotype data, undertook related data handling and calculation, managed recruitment and obtained biological samples. The following authors from the various collaborating groups undertook assembly of case/control series in their respective regions and collected data and samples: F.-R.Z. and B.-Q.Y. in Shandong province; X.-M.P. and W.-D.W. in Xinjiang Uygur Autonomous Region; F.H. in Chongqing city; X.-Q.Y. and J.-Z.Z. in Beijing city; C.-D.H. and X.-M.L. in Liaoning province; Y.-Z.L. in Heilongjiang province; L.-M.X. in Tianjin city; B.-H.J. in Wuhu city; J.Z. in Shanghai city; L.-D.S., C.Z., Q.-Y.F., F.-S.Z. Y.-L.C., J.-W.H., C.Q., B.C., H.-J.H., H.-F.W., W.H. performed the two-stage genotyping and sequencing. F.-Y.Z., H.-F.Z. and X.-Y.L. undertook data manipulation, statistical analysis and bio-informatic interrogations. All authors contributed to the final paper, with X.-J.Z., S.Y., J.-J.L., F.-Y.Z., L.-D.S. and C.Z. playing key roles.

Corresponding author

Correspondence to Xue-Jun Zhang.

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https://doi.org/10.1038/ng.310

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