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

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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Figure 1: Genome-wide association results from the initial GWAS analysis.
Figure 2: Association evidence within the MHC region from the stage 1 GWAS analysis.
Figure 3: The LD patterns of the LCE gene cluster region on 1q21 in populations of Chinese and European ancestry.

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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.).

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Authors

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.

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Correspondence to Xue-Jun Zhang.

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Supplementary Figures 1–3, Supplementary Tables 1 and 2 and Supplementary Methods (PDF 722 kb)

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Zhang, XJ., Huang, W., Yang, S. et al. Psoriasis genome-wide association study identifies susceptibility variants within LCE gene cluster at 1q21. Nat Genet 41, 205–210 (2009). https://doi.org/10.1038/ng.310

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