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Association analyses identify six new psoriasis susceptibility loci in the Chinese population

Abstract

We extended our previous genome-wide association study for psoriasis with a multistage replication study including 8,312 individuals with psoriasis (cases) and 12,919 controls from China as well as 3,293 cases and 4,188 controls from Germany and the United States and 254 nuclear families from the United States. We identified six new susceptibility loci associated with psoriasis in the Chinese study containing the candidate genes ERAP1, PTTG1, CSMD1, GJB2, SERPINB8 and ZNF816A (combined P < 5 × 10−8) and replicated one locus, 5q33.1 (TNIP1-ANXA6), previously reported (combined P = 3.8 × 10−21) in the European studies. Two of these loci showed evidence for association in the German study at ZNF816A and GJB2 with P = 3.6 × 10−3 and P = 7.9 × 10−3, respectively. ERAP1 and ZNF816A were associated with type 1 (early onset) psoriasis in the Chinese Han population (test for heterogeneity P = 6.5 × 10−3 and P = 1.5 × 10−3, respectively). Comparisons with the results of previous GWAS of psoriasis highlight the heterogeneity of disease susceptibility between the Chinese and European populations. Our study identifies new genetic susceptibility factors and suggests new biological pathways in psoriasis.

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Figure 1: Experimental design.

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Acknowledgements

We thank the individuals and their families who participated in this project; the study staff; S.-H. Duan for her contribution to the genotyping; and X.-B. Zuo for his help in creating the GWAS database, the data processing and the statistical analysis. This study was funded by the High-Tech Research and Development Program of China (863 Plan) (2007AA02Z161), the Key Project of Natural Science Foundation of China (30530670), Anhui Provincial Special Scientific Program (2007-7), the National Basic Research Program of China (973 Plan) (2007B516801), the General Program of National Natural Science Foundation of China (30771196, 30771942, 30800990, 81072461, 81071285, 30972727, 30800610 and 81000691), US National Institutes of Health (NIH) grant R01AR050266 (to A.M.B.), NIH grants R01AR42742, R01AR050511 and R01AR054966 (to J.T.E.), the German Ministry of Education and Research through the National Genome Research Network (BMFT 01GS 0171/ BMBF NUW-S23T10), the National Psoriasis Foundation of the US and the Agency for Science, Technology and Research of Singapore.

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Contributions

X.-J.Z. conceived of this study and obtained financial support. X.-J.Z., S.Y. and L.-D.S. designed the study. H.C., Z.-X.W., A.-P.Z. and P.-G.W. participated in the study design and were responsible for sample selection, genotyping and project management. J.T.E., A.F., A.M.B., J.-H.X., Q.-X.Z., F.-R.Z., X.-M.P., X.-Q.Y., J.-Z.Z., A.-E.X., R.-N.W., L.-M.X., M.W., G.-S.L., Z.-M.L., H.-M.G., W.-Z.Y., Cheng Zhang, B.-Q.Y., Y.-Y.S., S.-S.L., Y.L., J.-H.J., C.-T.L., R.-X.C., X.J., P.Z., W.-M.S., J.T., H.-Q.Z., L.S., J. Cui, J. Cheng, L.-J.Z., B.T., F.H., Q.Q., X.-P.P., A.-M.Z., L.-M.S. and J.-L.L. conducted sample selection and data management, undertook recruitment, collected phenotype data, undertook related data handling and calculation, managed recruitment and obtained biological samples. S.-M.Z., H.-Y.W., X.F., G.C., P.L., J.Z., H.-S.Z., T.T. and S.-K.S. performed genotyping analysis. Y.-Q.R., Chi Zhang, R.P.N., P.E.S., E.E., J.-J.L., F.-Y.Z. and W.-D.D. undertook data processing, statistical analysis and bioinformatics investigations. C.A.H. performed analyses and designed genotyping assays for the 254 nuclear families, which was performed by L.P. and A.M.B. All the authors contributed to the final paper, with X.-J.Z., S.Y., L.-D.S., H.C., Z.-X.W., J.T.E., P.E.S., A.M.B., A.F., A.-P.Z. and P.-G.W. playing key roles.

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Correspondence to Xue-Jun Zhang.

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Supplementary Figures 1 and 2 and Supplementary Tables 1–6. (PDF 650 kb)

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Sun, LD., Cheng, H., Wang, ZX. et al. Association analyses identify six new psoriasis susceptibility loci in the Chinese population. Nat Genet 42, 1005–1009 (2010). https://doi.org/10.1038/ng.690

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