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Genome-wide association analysis identifies three psoriasis susceptibility loci

Nature Genetics volume 42, pages 1000–1004 (2010)Cite this article

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Abstract

We carried out a meta-analysis of two recent psoriasis genome-wide association studies1,2 with a combined discovery sample of 1,831 affected individuals (cases) and 2,546 controls. One hundred and two loci selected based on P value rankings were followed up in a three-stage replication study including 4,064 cases and 4,685 controls from Michigan, Toronto, Newfoundland and Germany. In the combined meta-analysis, we identified three new susceptibility loci, including one at NOS2 (rs4795067, combined P = 4 × 10−11), one at FBXL19 (rs10782001, combined P = 9 × 10−10) and one near PSMA6-NFKBIA (rs12586317, combined P = 2 × 10−8). All three loci were also associated with psoriatic arthritis (rs4795067, combined P = 1 × 10−5; rs10782001, combined P = 4 × 10−8; and rs12586317, combined P = 6 × 10−5) and purely cutaneous psoriasis (rs4795067, combined P = 1 × 10−8; rs10782001, combined P = 2 × 10−6; and rs12586317, combined P = 1 × 10−6). We also replicated a recently identified3 association signal near RNF114 (rs495337, combined P = 2 × 10−7).

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Figure 1: Evidence for psoriasis association in four genomic regions including the three new loci attaining genome-wide significance and the confirmed RNF114 region.
Figure 2: Expression data for notable candidate genes within the three psoriasis-associated regions.

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Acknowledgements

The authors wish to thank the many psoriasis and PsA cases and normal controls who participated in this study and to acknowledge the key contributions of K. Callis Duffin, D. Goldgar and B. Jian Feng of the University of Utah and C. Helms of Washington University at St. Louis to the CASP study. This research was supported by grants R01AR42742, R01AR050511, R01AR054966, R01AR050266, R01HG002651 and U01HG005214 from the US National Institutes of Health, by the Ann Arbor Veterans Affairs Hospital, by the German Ministry of Education and Research through the National Genome Research Network (BMFT 01GS 0171/ BMBF NUW-S23T10) and by the Krembil Foundation and the Canadian Institutes of Health Research.

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Author notes

  1. Philip E Stuart and Rajan P Nair: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Dermatology, University of Michigan Medical School, Ann Arbor, Michigan, USA

    Philip E Stuart, Rajan P Nair, Trilokraj Tejasvi, Johann E Gudjonsson, John J Voorhees & James T Elder

  2. Institute for Clinical Molecular Biology, University of Kiel, Kiel, Germany

    Eva Ellinghaus & Andre Franke

  3. Department of Biostatistics, Center for Statistical Genetics, School of Public Health, University of Michigan, Ann Arbor, Michigan, USA

    Jun Ding, Yun Li & Gonçalo R Abecasis

  4. Department of Dermatology and Allergy, Technical University Munich, Munich, Germany

    Stephan Weidinger & Bernadette Eberlein

  5. Institute of Medical Informatics, Biometry and Epidemiology, Ludwig-Maximilians-University, Munich, Germany

    Christian Gieger & H Erich Wichmann

  6. Comprehensive Center for Inflammation Medicine, University of Lübeck, Lübeck, Germany

    Manfred Kunz

  7. Department of Medicine, University of Michigan Medical School, Ann Arbor, Michigan, USA

    Robert Ike

  8. Department of Dermatology, University of Utah, Salt Lake City, Utah, USA

    Gerald G Krueger

  9. Division of Human Genetics, Department of Genetics, Washington University at St. Louis, St. Louis, Missouri, USA

    Anne M Bowcock

  10. Department of Dermatology, University of Kiel, Kiel, Germany

    Ulrich Mrowietz & Michael Weichenthal

  11. Department of Dermatology, Henry Ford Hospital, Detroit, Michigan, USA

    Henry W Lim

  12. Department of Medicine, Memorial University, St. John's, Newfoundland, Canada

    Proton Rahman

  13. Department of Rheumatology, University of Toronto, Toronto, Ontario, Canada

    Dafna D Gladman

  14. Ann Arbor Veterans Affairs Medical Center, Ann Arbor, Michigan, USA

    James T Elder

Authors
  1. Philip E Stuart
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Contributions

R.P.N., P.E.S. and J.T.E. performed SNP selection, data analysis and prepared the figures and tables. R.P.N., T.T., P.E.S., P.R. and E.E. performed genotyping. P.E.S., Y.L. and J.D. performed genotype imputation and association analyses, and P.E.S., J.E.G., and J.D. performed the expression analyses. G.R.A. helped with statistical analyses and interpretation of results. R.P.N., T.T., J.J.V., R.I., M.W., S.W., B.E., C.G., H.E.W., H.W.L., P.R., M.K., U.M. and D.D.G. coordinated subject recruitment and collected phenotype data. J.T.E., G.G.K. and A.M.B. contributed genotypes and phenotypes from the CASP discovery GWAS. J.T.E. and P.E.S. drafted the manuscript; R.P.N., G.R.A., E.E., M.W. and A.F. edited the manuscript; and J.T.E. planned and supervised the study. All authors approved the final draft.

Corresponding author

Correspondence to James T Elder.

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The authors declare no competing financial interests.

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Supplementary Tables 1–6 and Supplementary Figures 1 and 2. (PDF 2747 kb)

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Stuart, P., Nair, R., Ellinghaus, E. et al. Genome-wide association analysis identifies three psoriasis susceptibility loci. Nat Genet 42, 1000–1004 (2010). https://doi.org/10.1038/ng.693

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