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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References
Bhalerao, J. & Bowcock, A.M. The genetics of psoriasis: a complex disorder of the skin and immune system. Hum. Mol. Genet. 7, 1537–1545 (1998).
Cargill, M. et al. A large-scale genetic association study confirms IL12B and leads to the identification of IL23R as psoriasis-risk genes. Am. J. Hum. Genet. 80, 273–290 (2007).
Simons, R.D. Additional studies on psoriasis in the tropics and in starvation camps. J. Invest. Dermatol. 12, 285–294 (1949).
Yip, S.Y. The prevalence of psoriasis in the Mongoloid race. J. Am. Acad. Dermatol. 10, 965–968 (1984).
Henseler, T. & Christophers, E. Psoriasis of early and late onset: characterization of two types of psoriasis vulgaris. J. Am. Acad. Dermatol. 13, 450–456 (1985).
Zhang, X., Wang, H., Te-Shao, H., Yang, S. & Chen, S. The genetic epidemiology of psoriasis vulgaris in Chinese Han. Int. J. Dermatol. 41, 663–669 (2002).
Nair, R.P. et al. Sequence and haplotype analysis supports HLA-C as the psoriasis susceptibility 1 gene. Am. J. Hum. Genet. 78, 827–851 (2006).
Fan, X. et al. Fine mapping of the psoriasis susceptibility locus PSORS1 supports HLA-C as the susceptibility gene in the Han Chinese population. PLoS Genet. 4, e1000038 (2008).
Schön, M.P. & Boehncke, W.H. Psoriasis. N. Engl. J. Med. 352, 1899–1912 (2005).
Zhang, X.J. et al. Polymorphisms in interleukin-15 gene on chromosome 4q31.2 are associated with psoriasis vulgaris in Chinese population. J. Invest. Dermatol. 127, 2544–2551 (2007).
Liu, Y. et al. A genome-wide association study of psoriasis and psoriatic arthritis identifies new disease loci. PLoS Genet. 4, e1000041 (2008).
Bowcock, A.M. Psoriasis genetics: the way forward. J. Invest. Dermatol. 122, xv–xvii (2004).
Lesueur, F. et al. ADAM33, a new candidate for psoriasis susceptibility. PLoS ONE 2, e906 (2007).
Capon, F. et al. Identification of ZNF313/RNF114 as a novel psoriasis susceptibility gene. Hum. Mol. Genet. 17, 1938–1945 (2008).
Capon, F. et al. Sequence variants in the genes for the interleukin-23 receptor (IL23R) and its ligand (IL12B) confer protection against psoriasis. Hum. Genet. 122, 201–206 (2007).
Chang, Y.T. et al. Cytokine gene polymorphisms in Chinese patients with psoriasis. Br. J. Dermatol. 156, 899–905 (2007).
Tsunemi, Y. et al. Interleukin-12 p40 gene (IL12B) 3′-untranslated region polymorphism is associated with susceptibility to atopic dermatitis and psoriasis vulgaris. J. Dermatol. Sci. 30, 161–166 (2002).
Backendorf, C. & Hohl, D. A common origin for cornified envelope proteins? Nat. Genet. 2, 91 (1992).
Engelkamp, D., Schafer, B.W., Mattei, M.G., Erne, P. & Heizmann, C.W. Six S100 genes are clustered on human chromosome 1q21: identification of two genes coding for the two previously unreported calcium-binding proteins S100D and S100E. Proc. Natl. Acad. Sci. USA 90, 6547–6551 (1993).
Mischke, D., Korge, B.P., Marenholz, I., Volz, A. & Ziegler, A. Genes encoding structural proteins of epidermal cornification and S100 calcium-binding proteins form a gene complex (“epidermal differentiation complex”) on human chromosome 1q21. J. Invest. Dermatol. 106, 989–992 (1996).
Wang, A., Johnson, D.G. & MacLeod, M.C. Molecular cloning and characterization of a novel mouse epidermal differentiation gene and its promoter. Genomics 73, 284–290 (2001).
Bowcock, A.M. & Krueger, J.G. Getting under the skin: the immunogenetics of psoriasis. Nat. Rev. Immunol. 5, 699–711 (2005).
Krueger, J.G. & Bowcock, A. Psoriasis pathophysiology: current concepts of pathogenesis. Ann. Rheum. Dis. 64 (Suppl 2), ii30–ii36 (2005).
Purcell, S. et al. PLINK: a tool set for whole-genome association and population-based linkage analyses. Am. J. Hum. Genet. 81, 559–575 (2007).
Price, A.L. et al. Principal components analysis corrects for stratification in genome-wide association studies. Nat. Genet. 38, 904–909 (2006).
Mantel, N. & Haenszel, W. Statistical aspects of the analysis of data from retrospective studies of disease. J. Natl. Cancer Inst. 22, 719–748 (1959).
Garcia-Closas, M. et al. Heterogeneity of breast cancer associations with five susceptibility loci by clinical and pathological characteristics. PLoS Genet. 4, e1000054 (2008).
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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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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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). http://doi.org/10.1038/ng.310
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DOI: http://doi.org/10.1038/ng.310
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