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 Edkins & 31 others Xavier 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

    Research output: Contribution to journalArticle

    601 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., ... 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
    Strange, Amy ; Capon, Francesca ; Spencer, Chris C. A. ; Knight, Jo ; Weale, Michael E. ; Allen, Michael H. ; Barton, Anne ; Band, Gavin ; Bellenguez, Celine ; Bergboer, Judith G. M. ; Blackwell, Jenefer M. ; Bramon, Elvira ; Bumpstead, Suzannah J. ; Casas, Juan P. ; Cork, Michael J. ; Corvin, Aiden ; Deloukas, Panos ; Dilthey, Alexander ; Duncanson, Audrey ; Edkins, Sarah ; Estivill, Xavier ; Fitzgerald, Oliver ; Freeman, Colin ; Giardina, Emiliano ; Gray, Emma ; Hofer, Angelika ; Hüffmeier, Ulrike ; Hunt, Sarah E. ; Irvine, Alan D. ; Jankowski, Janusz ; Kirby, Brian ; Langford, Cordelia ; Lascorz, Jesus ; Leman, Joyce ; Leslie, Stephen ; Mallbris, Lotus ; Markus, Hugh S. ; Mathew, Christopher G. ; McLean, W. H. Irwin ; McManus, Ross ; Mössner, Rotraut ; Moutsianas, Loukas ; Naluai, Asa T. ; Nestle, Frank O. ; Novelli, Giuseppe ; Onoufriadis, Alexandros ; Palmer, Colin N. A. ; Perricone, Carlo ; Pirinen, Matti ; Plomin, Robert ; Genetic Anal Psoriasis Consortium, Wellcome Trust Case Control. / A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. In: Nature Genetics. 2010 ; Vol. 42, No. 11. pp. 985-990.
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    title = "A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1",
    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.",
    keywords = "STATISTICAL-METHOD, DISEASES, GENE, VARIANTS, AUTOIMMUNITY, RESPONSES, PATHWAYS, COMPLEX, FAMILY, SCAN",
    author = "Amy Strange and Francesca Capon and Spencer, {Chris C. A.} and Jo Knight and Weale, {Michael E.} and Allen, {Michael H.} and Anne Barton and Gavin Band and Celine Bellenguez and Bergboer, {Judith G. M.} and Blackwell, {Jenefer M.} and Elvira Bramon and Bumpstead, {Suzannah J.} and Casas, {Juan P.} and Cork, {Michael J.} and Aiden Corvin and Panos Deloukas and Alexander Dilthey and Audrey Duncanson and Sarah Edkins and Xavier Estivill and Oliver Fitzgerald and Colin Freeman and Emiliano Giardina and Emma Gray and Angelika Hofer and Ulrike H{\"u}ffmeier and Hunt, {Sarah E.} and Irvine, {Alan D.} and Janusz Jankowski and Brian Kirby and Cordelia Langford and Jesus Lascorz and Joyce Leman and Stephen Leslie and Lotus Mallbris and Markus, {Hugh S.} and Mathew, {Christopher G.} and McLean, {W. H. Irwin} and Ross McManus and Rotraut M{\"o}ssner and Loukas Moutsianas and Naluai, {Asa T.} and Nestle, {Frank O.} and Giuseppe Novelli and Alexandros Onoufriadis and Palmer, {Colin N. A.} and Carlo Perricone and Matti Pirinen and Robert Plomin and {Genetic Anal Psoriasis Consortium, Wellcome Trust Case Control}",
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    pages = "985--990",
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    Strange, A, Capon, F, Spencer, CCA, Knight, J, Weale, ME, Allen, MH, Barton, A, Band, G, Bellenguez, C, Bergboer, JGM, Blackwell, JM, Bramon, E, Bumpstead, SJ, Casas, JP, Cork, MJ, Corvin, A, Deloukas, P, Dilthey, A, Duncanson, A, Edkins, S, Estivill, X, Fitzgerald, O, Freeman, C, Giardina, E, Gray, E, Hofer, A, Hüffmeier, U, Hunt, SE, Irvine, AD, Jankowski, J, Kirby, B, Langford, C, Lascorz, J, Leman, J, Leslie, S, Mallbris, L, Markus, HS, Mathew, CG, McLean, WHI, McManus, R, Mössner, R, Moutsianas, L, Naluai, AT, Nestle, FO, Novelli, G, Onoufriadis, A, Palmer, CNA, Perricone, C, Pirinen, M, Plomin, R & 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, vol. 42, no. 11, pp. 985-990. https://doi.org/10.1038/ng.694

    A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1. / Strange, Amy; Capon, Francesca; Spencer, Chris C. A.; Knight, Jo; Weale, Michael E.; Allen, Michael H.; Barton, Anne; Band, Gavin; Bellenguez, Celine; Bergboer, Judith G. M.; Blackwell, Jenefer M.; Bramon, Elvira; Bumpstead, Suzannah J.; Casas, Juan P.; Cork, Michael J.; Corvin, Aiden; Deloukas, Panos; Dilthey, Alexander; Duncanson, Audrey; Edkins, Sarah; Estivill, Xavier; Fitzgerald, Oliver; Freeman, Colin; Giardina, Emiliano; Gray, Emma; Hofer, Angelika; Hüffmeier, Ulrike; Hunt, Sarah E.; Irvine, Alan D.; Jankowski, Janusz; Kirby, Brian; Langford, Cordelia; Lascorz, Jesus; Leman, Joyce; Leslie, Stephen; Mallbris, Lotus; Markus, Hugh S.; Mathew, Christopher G.; McLean, W. H. Irwin; McManus, Ross; Mössner, Rotraut; Moutsianas, Loukas; Naluai, Asa T.; Nestle, Frank O.; Novelli, Giuseppe; Onoufriadis, Alexandros; Palmer, Colin N. A.; Perricone, Carlo; Pirinen, Matti; Plomin, Robert; Genetic Anal Psoriasis Consortium, Wellcome Trust Case Control.

    In: Nature Genetics, Vol. 42, No. 11, 11.2010, p. 985-990.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - A genome-wide association study identifies new psoriasis susceptibility loci and an interaction between HLA-C and ERAP1

    AU - Strange, Amy

    AU - Capon, Francesca

    AU - Spencer, Chris C. A.

    AU - Knight, Jo

    AU - Weale, Michael E.

    AU - Allen, Michael H.

    AU - Barton, Anne

    AU - Band, Gavin

    AU - Bellenguez, Celine

    AU - Bergboer, Judith G. M.

    AU - Blackwell, Jenefer M.

    AU - Bramon, Elvira

    AU - Bumpstead, Suzannah J.

    AU - Casas, Juan P.

    AU - Cork, Michael J.

    AU - Corvin, Aiden

    AU - Deloukas, Panos

    AU - Dilthey, Alexander

    AU - Duncanson, Audrey

    AU - Edkins, Sarah

    AU - Estivill, Xavier

    AU - Fitzgerald, Oliver

    AU - Freeman, Colin

    AU - Giardina, Emiliano

    AU - Gray, Emma

    AU - Hofer, Angelika

    AU - Hüffmeier, Ulrike

    AU - Hunt, Sarah E.

    AU - Irvine, Alan D.

    AU - Jankowski, Janusz

    AU - Kirby, Brian

    AU - Langford, Cordelia

    AU - Lascorz, Jesus

    AU - Leman, Joyce

    AU - Leslie, Stephen

    AU - Mallbris, Lotus

    AU - Markus, Hugh S.

    AU - Mathew, Christopher G.

    AU - McLean, W. H. Irwin

    AU - McManus, Ross

    AU - Mössner, Rotraut

    AU - Moutsianas, Loukas

    AU - Naluai, Asa T.

    AU - Nestle, Frank O.

    AU - Novelli, Giuseppe

    AU - Onoufriadis, Alexandros

    AU - Palmer, Colin N. A.

    AU - Perricone, Carlo

    AU - Pirinen, Matti

    AU - Plomin, Robert

    AU - Genetic Anal Psoriasis Consortium, Wellcome Trust Case Control

    PY - 2010/11

    Y1 - 2010/11

    N2 - 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.

    AB - 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.

    KW - STATISTICAL-METHOD

    KW - DISEASES

    KW - GENE

    KW - VARIANTS

    KW - AUTOIMMUNITY

    KW - RESPONSES

    KW - PATHWAYS

    KW - COMPLEX

    KW - FAMILY

    KW - SCAN

    U2 - 10.1038/ng.694

    DO - 10.1038/ng.694

    M3 - Article

    VL - 42

    SP - 985

    EP - 990

    JO - Nature Genetics

    JF - Nature Genetics

    SN - 1061-4036

    IS - 11

    ER -