A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1

Amy Strange, Francesca Capon, Chris C. A. Spencer, Jo Knight, Michael E. Weale, Michael H. Allen, Anne Barton, Gavin Band, Celine Bellenguez, Judith G. M. Bergboer, Jenefer M. Blackwell, Elvira Bramon, Suzannah J. Bumpstead, Juan P. Casas, Michael J. Cork, Aiden Corvin, Panos Deloukas, Alexander Dilthey, Audrey Duncanson, Sarah EdkinsXavier Estivill, Oliver Fitzgerald, Colin Freeman, Emiliano Giardina, Emma Gray, Angelika Hofer, Ulrike Hüffmeier, Sarah E. Hunt, Alan D. Irvine, Janusz Jankowski, Brian Kirby, Cordelia Langford, Jesus Lascorz, Joyce Leman, Stephen Leslie, Lotus Mallbris, Hugh S. Markus, Christopher G. Mathew, W. H. Irwin McLean, Ross McManus, Rotraut Mössner, Loukas Moutsianas, Asa T. Naluai, Frank O. Nestle, Giuseppe Novelli, Alexandros Onoufriadis, Colin N. A. Palmer, Carlo Perricone, Matti Pirinen, Robert Plomin, Genetic Anal Psoriasis Consortium, Wellcome Trust Case Control

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    650 Citations (Scopus)

    Abstract

    To identify new susceptibility loci for psoriasis, we undertook a genome-wide association study of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls. We identified associations at eight previously unreported genomic loci. Seven loci harbored genes with recognized immune functions (IL28RA, REL, IFIH1, ERAP1, TRAF3IP2, NFKBIA and TYK2). These associations were replicated in 9,079 European samples (six loci with a combined P < 5 x 10(-8) and two loci with a combined P < 5 x 10(-7)). We also report compelling evidence for an interaction between the HLA-C and ERAP1 loci (combined P = 6.95 x 10(-6)). ERAP1 plays an important role in MHC class I peptide processing. ERAP1 variants only influenced psoriasis susceptibility in individuals carrying the HLA-C risk allele. Our findings implicate pathways that integrate epidermal barrier dysfunction with innate and adaptive immune dysregulation in psoriasis pathogenesis.

    Original languageEnglish
    Pages (from-to)985-990
    Number of pages6
    JournalNature Genetics
    Volume42
    Issue number11
    DOIs
    Publication statusPublished - Nov 2010

    Keywords

    • STATISTICAL-METHOD
    • DISEASES
    • GENE
    • VARIANTS
    • AUTOIMMUNITY
    • RESPONSES
    • PATHWAYS
    • COMPLEX
    • FAMILY
    • SCAN

    Cite this

    Strange, A., Capon, F., Spencer, C. C. A., Knight, J., Weale, M. E., Allen, M. H., Barton, A., Band, G., Bellenguez, C., Bergboer, J. G. M., Blackwell, J. M., Bramon, E., Bumpstead, S. J., Casas, J. P., Cork, M. J., Corvin, A., Deloukas, P., Dilthey, A., Duncanson, A., ... Genetic Anal Psoriasis Consortium, Wellcome Trust Case Control (2010). A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. Nature Genetics, 42(11), 985-990. https://doi.org/10.1038/ng.694