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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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.

Author information

Author notes

    • Philip E Stuart
    •  & Rajan P Nair

    These authors contributed equally to this work.

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. Center for Statistical Genetics, Department of Biostatistics, 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

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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.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to James T Elder.

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DOI

https://doi.org/10.1038/ng.693

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