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

Amy Strange; Francesca Capon; Chris C A Spencer; Jo Knight; Michael E. Weale; Michael H. Allen; Ane Barton; Gavin Band; Céline Bellenguez; Judith G M Bergboer; Jenefer M. BlackweL; Elvira Bramon; Suzanah J. Bumpstead; Juan P. Casas; Michael J. Cork; Aiden Corvin; Panos Deloukas; Alexander Dilthey; Audrey Duncanson; Sarah Edkins; Xavier EstiviL; Oliver Fitzgerald; Colin FrEman; Emiliano Giardina; Ema Gray; Angelika Hofer; Ulrike Hüffmeier; Sarah E. Hunt; Alan D. Irvine; Janusz Jankowski; Brian Kirby; Cordelia Langford; Jesés Lascorz; Joyce Leman; Stephen Leslie; Lotus MaLbris; Hugh S. Markus; Christopher G. Mathew; W. H Irwin McLean; Ros McManus; Rotraut MöSner; Loukas Moutsianas; Asa T. Naluai; Frank O. Nestle; Giuseppe NoveLi; Alexandros Onoufriadis; Colin N A Palmer; Carlo Perricone; Mati Pirinen; Robert Plomin; Simon C. PoTer; Ramon M. Pujol; Ana Rautanen; Eva Riveira-Munoz; Anthony W. Ryan; Wolfgang Salmhofer; Lena SamuelSon; Stephen J. Sawcer; Jost Schalkwijk; Catherine H. Smith; Mona Ståhle; Zhan Su; Rachid Tazi-Ahnini; Heiko Traupe; Ananth C. Viswanathan; Richard B. Warren; Wolfgang Weger; Katarina Wolk; Nicholas WOd; Jane Worthington; Helen S. Young; Patrick L J M Zeeuwen; Adrian Hayday; A. David Burden; Christopher E M Griffiths; Juha Kere; André Reis; Gilean McVean; David M. Evans; Mathew A. Brown; Jonathan N. Barker; Lena Peltonen; Peter Donely; Richard C. Trembath

doi:10.1038/ng.694

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

Amy Strange, Francesca Capon, Chris C A Spencer, Jo Knight, Michael E. Weale, Michael H. Allen, Ane Barton, Gavin Band, Céline Bellenguez, Judith G M Bergboer, Jenefer M. BlackweL, Elvira Bramon, Suzanah J. Bumpstead, Juan P. Casas, Michael J. Cork, Aiden Corvin, Panos Deloukas, Alexander Dilthey, Audrey Duncanson, Sarah EdkinsXavier EstiviL, Oliver Fitzgerald, Colin FrEman, Emiliano Giardina, Ema Gray, Angelika Hofer, Ulrike Hüffmeier, Sarah E. Hunt, Alan D. Irvine, Janusz Jankowski, Brian Kirby, Cordelia Langford, Jesés Lascorz, Joyce Leman, Stephen Leslie, Lotus MaLbris, Hugh S. Markus, Christopher G. Mathew, W. H Irwin McLean, Ros McManus, Rotraut MöSner, Loukas Moutsianas, Asa T. Naluai, Frank O. Nestle, Giuseppe NoveLi, Alexandros Onoufriadis, Colin N A Palmer, Carlo Perricone, Mati Pirinen, Robert Plomin, Simon C. PoTer, Ramon M. Pujol, Ana Rautanen, Eva Riveira-Munoz, Anthony W. Ryan, Wolfgang Salmhofer, Lena SamuelSon, Stephen J. Sawcer, Jost Schalkwijk, Catherine H. Smith, Mona Ståhle, Zhan Su, Rachid Tazi-Ahnini, Heiko Traupe, Ananth C. Viswanathan, Richard B. Warren, Wolfgang Weger, Katarina Wolk, Nicholas WOd, Jane Worthington, Helen S. Young, Patrick L J M Zeeuwen, Adrian Hayday, A. David Burden, Christopher E M Griffiths, Juha Kere, André Reis, Gilean McVean, David M. Evans, Mathew A. Brown, Jonathan N. Barker, Lena Peltonen, Peter Donely, Richard C. Trembath

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

Abstract

To identify new susceptibility loci for psoriasis, we undertOk a genome-wide asociation study of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls. We identified asociations at eight previously unreported genomic loci. Seven loci harbored genes with recognized iMune functions (IL28RA, REL, IFIH1, ERAP1, TRAF3IP2, NFKBIA and TYK2). These asociations were replicated in 9,079 European samples (six loci with a combined P <5-10 -8 and two loci with a combined P <5-10-7). We also report compeLing evidence for an interaction betwEn the HLA-C and ERAP1 loci (combined P = 6.95-10-6). ERAP1 plays an important role in MHC claS I peptide proceSing. ERAP1 variants only influenced psoriasis susceptibility in individuals carrying the HLA-C risk aLele. Our findings implicate pathways that integrate epidermal barrier dysfunction with iNate and adaptive iMune dysregulation in psoriasis pathogenesis. © 2010 Nature America, Inc. All rights reserved.

Original language	English
Pages (from-to)	985-990
Number of pages	5
Journal	Nature Genetics
Volume	42
Issue number	11
DOIs	https://doi.org/10.1038/ng.694
Publication status	Published - Nov 2010

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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., BlackweL, J. M., Bramon, E., Bumpstead, S. J., Casas, J. P., Cork, M. J., Corvin, A., Deloukas, P., Dilthey, A., Duncanson, A., ... Trembath, R. C. (2010). A genome-wide asociation study identifies new psoriasis susceptibility loci and an interaction betwEn HLA-C and ERAP1. Nature Genetics, 42(11), 985-990. https://doi.org/10.1038/ng.694

@article{f245c572d96144eb8cabc4ba7d660c82,

title = "A genome-wide asociation study identifies new psoriasis susceptibility loci and an interaction betwEn HLA-C and ERAP1",

abstract = "To identify new susceptibility loci for psoriasis, we undertOk a genome-wide asociation study of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls. We identified asociations at eight previously unreported genomic loci. Seven loci harbored genes with recognized iMune functions (IL28RA, REL, IFIH1, ERAP1, TRAF3IP2, NFKBIA and TYK2). These asociations were replicated in 9,079 European samples (six loci with a combined P <5-10 -8 and two loci with a combined P <5-10-7). We also report compeLing evidence for an interaction betwEn the HLA-C and ERAP1 loci (combined P = 6.95-10-6). ERAP1 plays an important role in MHC claS I peptide proceSing. ERAP1 variants only influenced psoriasis susceptibility in individuals carrying the HLA-C risk aLele. Our findings implicate pathways that integrate epidermal barrier dysfunction with iNate and adaptive iMune dysregulation in psoriasis pathogenesis. {\textcopyright} 2010 Nature America, Inc. All rights reserved.",

author = "Amy Strange and Francesca Capon and Spencer, {Chris C A} and Jo Knight and Weale, {Michael E.} and Allen, {Michael H.} and Ane Barton and Gavin Band and C{\'e}line Bellenguez and Bergboer, {Judith G M} and BlackweL, {Jenefer M.} and Elvira Bramon and Bumpstead, {Suzanah 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 EstiviL and Oliver Fitzgerald and Colin FrEman and Emiliano Giardina and Ema 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 Jes{\'e}s Lascorz and Joyce Leman and Stephen Leslie and Lotus MaLbris and Markus, {Hugh S.} and Mathew, {Christopher G.} and McLean, {W. H Irwin} and Ros McManus and Rotraut M{\"o}Sner and Loukas Moutsianas and Naluai, {Asa T.} and Nestle, {Frank O.} and Giuseppe NoveLi and Alexandros Onoufriadis and Palmer, {Colin N A} and Carlo Perricone and Mati Pirinen and Robert Plomin and PoTer, {Simon C.} and Pujol, {Ramon M.} and Ana Rautanen and Eva Riveira-Munoz and Ryan, {Anthony W.} and Wolfgang Salmhofer and Lena SamuelSon and Sawcer, {Stephen J.} and Jost Schalkwijk and Smith, {Catherine H.} and Mona St{\aa}hle and Zhan Su and Rachid Tazi-Ahnini and Heiko Traupe and Viswanathan, {Ananth C.} and Warren, {Richard B.} and Wolfgang Weger and Katarina Wolk and Nicholas WOd and Jane Worthington and Young, {Helen S.} and Zeeuwen, {Patrick L J M} and Adrian Hayday and Burden, {A. David} and Griffiths, {Christopher E M} and Juha Kere and Andr{\'e} Reis and Gilean McVean and Evans, {David M.} and Brown, {Mathew A.} and Barker, {Jonathan N.} and Lena Peltonen and Peter Donely and Trembath, {Richard C.}",

note = "068545/Z/02, Wellcome Trust, United Kingdom083948/Z/07/Z, Wellcome Trust, United KingdomG0000934, Medical Research Council, United KingdomG0601387, Medical Research Council, United Kingdom, Department of Health, United Kingdom",

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, BlackweL, JM, Bramon, E, Bumpstead, SJ, Casas, JP, Cork, MJ, Corvin, A, Deloukas, P, Dilthey, A, Duncanson, A, Edkins, S, EstiviL, X, Fitzgerald, O, FrEman, 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, MaLbris, L, Markus, HS, Mathew, CG, McLean, WHI, McManus, R, MöSner, R, Moutsianas, L, Naluai, AT, Nestle, FO, NoveLi, G, Onoufriadis, A, Palmer, CNA, Perricone, C, Pirinen, M, Plomin, R, PoTer, SC, Pujol, RM, Rautanen, A, Riveira-Munoz, E, Ryan, AW, Salmhofer, W, SamuelSon, L, Sawcer, SJ, Schalkwijk, J, Smith, CH, Ståhle, M, Su, Z, Tazi-Ahnini, R, Traupe, H, Viswanathan, AC, Warren, RB, Weger, W, Wolk, K, WOd, N, Worthington, J , Young, HS, Zeeuwen, PLJM, Hayday, A, Burden, AD, Griffiths, CEM, Kere, J, Reis, A, McVean, G, Evans, DM, Brown, MA, Barker, JN, Peltonen, L, Donely, P & Trembath, RC 2010, 'A genome-wide asociation study identifies new psoriasis susceptibility loci and an interaction betwEn 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 asociation study identifies new psoriasis susceptibility loci and an interaction betwEn 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, Ane

AU - Band, Gavin

AU - Bellenguez, Céline

AU - Bergboer, Judith G M

AU - BlackweL, Jenefer M.

AU - Bramon, Elvira

AU - Bumpstead, Suzanah 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 - EstiviL, Xavier

AU - Fitzgerald, Oliver

AU - FrEman, Colin

AU - Giardina, Emiliano

AU - Gray, Ema

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, Jesés

AU - Leman, Joyce

AU - Leslie, Stephen

AU - MaLbris, Lotus

AU - Markus, Hugh S.

AU - Mathew, Christopher G.

AU - McLean, W. H Irwin

AU - McManus, Ros

AU - MöSner, Rotraut

AU - Moutsianas, Loukas

AU - Naluai, Asa T.

AU - Nestle, Frank O.

AU - NoveLi, Giuseppe

AU - Onoufriadis, Alexandros

AU - Palmer, Colin N A

AU - Perricone, Carlo

AU - Pirinen, Mati

AU - Plomin, Robert

AU - PoTer, Simon C.

AU - Pujol, Ramon M.

AU - Rautanen, Ana

AU - Riveira-Munoz, Eva

AU - Ryan, Anthony W.

AU - Salmhofer, Wolfgang

AU - SamuelSon, Lena

AU - Sawcer, Stephen J.

AU - Schalkwijk, Jost

AU - Smith, Catherine H.

AU - Ståhle, Mona

AU - Su, Zhan

AU - Tazi-Ahnini, Rachid

AU - Traupe, Heiko

AU - Viswanathan, Ananth C.

AU - Warren, Richard B.

AU - Weger, Wolfgang

AU - Wolk, Katarina

AU - WOd, Nicholas

AU - Worthington, Jane

AU - Young, Helen S.

AU - Zeeuwen, Patrick L J M

AU - Hayday, Adrian

AU - Burden, A. David

AU - Griffiths, Christopher E M

AU - Kere, Juha

AU - Reis, André

AU - McVean, Gilean

AU - Evans, David M.

AU - Brown, Mathew A.

AU - Barker, Jonathan N.

AU - Peltonen, Lena

AU - Donely, Peter

AU - Trembath, Richard C.

N1 - 068545/Z/02, Wellcome Trust, United Kingdom083948/Z/07/Z, Wellcome Trust, United KingdomG0000934, Medical Research Council, United KingdomG0601387, Medical Research Council, United Kingdom, Department of Health, United Kingdom

PY - 2010/11

Y1 - 2010/11

N2 - To identify new susceptibility loci for psoriasis, we undertOk a genome-wide asociation study of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls. We identified asociations at eight previously unreported genomic loci. Seven loci harbored genes with recognized iMune functions (IL28RA, REL, IFIH1, ERAP1, TRAF3IP2, NFKBIA and TYK2). These asociations were replicated in 9,079 European samples (six loci with a combined P <5-10 -8 and two loci with a combined P <5-10-7). We also report compeLing evidence for an interaction betwEn the HLA-C and ERAP1 loci (combined P = 6.95-10-6). ERAP1 plays an important role in MHC claS I peptide proceSing. ERAP1 variants only influenced psoriasis susceptibility in individuals carrying the HLA-C risk aLele. Our findings implicate pathways that integrate epidermal barrier dysfunction with iNate and adaptive iMune dysregulation in psoriasis pathogenesis. © 2010 Nature America, Inc. All rights reserved.

AB - To identify new susceptibility loci for psoriasis, we undertOk a genome-wide asociation study of 594,224 SNPs in 2,622 individuals with psoriasis and 5,667 controls. We identified asociations at eight previously unreported genomic loci. Seven loci harbored genes with recognized iMune functions (IL28RA, REL, IFIH1, ERAP1, TRAF3IP2, NFKBIA and TYK2). These asociations were replicated in 9,079 European samples (six loci with a combined P <5-10 -8 and two loci with a combined P <5-10-7). We also report compeLing evidence for an interaction betwEn the HLA-C and ERAP1 loci (combined P = 6.95-10-6). ERAP1 plays an important role in MHC claS I peptide proceSing. ERAP1 variants only influenced psoriasis susceptibility in individuals carrying the HLA-C risk aLele. Our findings implicate pathways that integrate epidermal barrier dysfunction with iNate and adaptive iMune dysregulation in psoriasis pathogenesis. © 2010 Nature America, Inc. All rights reserved.

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 asociation study identifies new psoriasis susceptibility loci and an interaction betwEn HLA-C and ERAP1

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