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; 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

doi:10.1038/ng.694

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

Research output: Contribution to journal › Article › peer-review

884 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 language	English
Pages (from-to)	985-990
Number of pages	6
Journal	Nature Genetics
Volume	42
Issue number	11
DOIs	https://doi.org/10.1038/ng.694
Publication status	Published - Nov 2010

Keywords

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

Access to Document

10.1038/ng.694

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

@article{20189178b60e4d1d8b3ebdc057650a66,

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}",

year = "2010",

month = nov,

doi = "10.1038/ng.694",

language = "English",

volume = "42",

pages = "985--990",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "11",

}

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

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

C2 - 20953190

SN - 1061-4036

VL - 42

SP - 985

EP - 990

JO - Nature Genetics

JF - Nature Genetics

IS - 11

ER -

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

Abstract

Keywords

Access to Document

Fingerprint

Cite this