Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity

Lam C Tsoi; Sarah L Spain; Jo Knight; Eva Ellinghaus; Philip E Stuart; Francesca Capon; Jun Ding; Yanming Li; Trilokraj Tejasvi; Johann E Gudjonsson; Hyun M Kang; Michael H Allen; Ross McManus; Giuseppe Novelli; Lena Samuelsson; Joost Schalkwijk; Mona Ståhle; A David Burden; Catherine H Smith; Michael J Cork; Xavier Estivill; Anne M Bowcock; Gerald G Krueger; Wolfgang Weger; Jane Worthington; Rachid Tazi-Ahnini; Frank O Nestle; Adrian Hayday; Per Hoffmann; Juliane Winkelmann; Cisca Wijmenga; Cordelia Langford; Sarah Edkins; Robert Andrews; Hannah Blackburn; Amy Strange; Gavin Band; Richard D Pearson; Damjan Vukcevic; Chris C A Spencer; Alexandros Onoufriadis; Michael E Weale; Linda E Campbell; Christopher G Mathew; Robert Plomin; Ananth C Viswanathan; Emma Gray; Paul Weston; Jonathan N W N Barker; Richard C Trembath; Collaborative Association Study of Psoriasis (CASP)

doi:10.1038/ng.2467

Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity

Lam C Tsoi, Sarah L Spain, Jo Knight, Eva Ellinghaus, Philip E Stuart, Francesca Capon, Jun Ding, Yanming Li, Trilokraj Tejasvi, Johann E Gudjonsson, Hyun M Kang, Michael H Allen, Ross McManus, Giuseppe Novelli, Lena Samuelsson, Joost Schalkwijk, Mona Ståhle, A David Burden, Catherine H Smith, Michael J CorkXavier Estivill, Anne M Bowcock, Gerald G Krueger, Wolfgang Weger, Jane Worthington, Rachid Tazi-Ahnini, Frank O Nestle, Adrian Hayday, Per Hoffmann, Juliane Winkelmann, Cisca Wijmenga, Cordelia Langford, Sarah Edkins, Robert Andrews, Hannah Blackburn, Amy Strange, Gavin Band, Richard D Pearson, Damjan Vukcevic, Chris C A Spencer, Alexandros Onoufriadis, Michael E Weale, Linda E Campbell, Christopher G Mathew, Robert Plomin, Ananth C Viswanathan, Emma Gray, Paul Weston, Jonathan N W N Barker, Richard C Trembath, Collaborative Association Study of Psoriasis (CASP)

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Abstract

To gain further insight into the genetic architecture of psoriasis, we conducted a meta-analysis of 3 genome-wide association studies (GWAS) and 2 independent data sets genotyped on the Immunochip, including 10,588 cases and 22,806 controls. We identified 15 new susceptibility loci, increasing to 36 the number associated with psoriasis in European individuals. We also identified, using conditional analyses, five independent signals within previously known loci. The newly identified loci shared with other autoimmune diseases include candidate genes with roles in regulating T-cell function (such as RUNX3, TAGAP and STAT3). Notably, they included candidate genes whose products are involved in innate host defense, including interferon-mediated antiviral responses (DDX58), macrophage activation (ZC3H12C) and nuclear factor (NF)-κB signaling (CARD14 and CARM1). These results portend a better understanding of shared and distinctive genetic determinants of immune-mediated inflammatory disorders and emphasize the importance of the skin in innate and acquired host defense.

Original language	English
Pages (from-to)	1341-1348
Number of pages	8
Journal	Nature Genetics
Volume	44
Issue number	12
DOIs	https://doi.org/10.1038/ng.2467
Publication status	Published - Dec 2012

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Tsoi, L. C., Spain, S. L., Knight, J., Ellinghaus, E., Stuart, P. E., Capon, F., Ding, J., Li, Y., Tejasvi, T., Gudjonsson, J. E., Kang, H. M., Allen, M. H., McManus, R., Novelli, G., Samuelsson, L., Schalkwijk, J., Ståhle, M., Burden, A. D., Smith, C. H., ... Collaborative Association Study of Psoriasis (CASP) (2012). Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity. Nature Genetics, 44(12), 1341-1348. https://doi.org/10.1038/ng.2467

@article{d169a24ca315406c8d79d5d6f4daee9d,

title = "Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity",

abstract = "To gain further insight into the genetic architecture of psoriasis, we conducted a meta-analysis of 3 genome-wide association studies (GWAS) and 2 independent data sets genotyped on the Immunochip, including 10,588 cases and 22,806 controls. We identified 15 new susceptibility loci, increasing to 36 the number associated with psoriasis in European individuals. We also identified, using conditional analyses, five independent signals within previously known loci. The newly identified loci shared with other autoimmune diseases include candidate genes with roles in regulating T-cell function (such as RUNX3, TAGAP and STAT3). Notably, they included candidate genes whose products are involved in innate host defense, including interferon-mediated antiviral responses (DDX58), macrophage activation (ZC3H12C) and nuclear factor (NF)-κB signaling (CARD14 and CARM1). These results portend a better understanding of shared and distinctive genetic determinants of immune-mediated inflammatory disorders and emphasize the importance of the skin in innate and acquired host defense.",

author = "Tsoi, {Lam C} and Spain, {Sarah L} and Jo Knight and Eva Ellinghaus and Stuart, {Philip E} and Francesca Capon and Jun Ding and Yanming Li and Trilokraj Tejasvi and Gudjonsson, {Johann E} and Kang, {Hyun M} and Allen, {Michael H} and Ross McManus and Giuseppe Novelli and Lena Samuelsson and Joost Schalkwijk and Mona St{\aa}hle and Burden, {A David} and Smith, {Catherine H} and Cork, {Michael J} and Xavier Estivill and Bowcock, {Anne M} and Krueger, {Gerald G} and Wolfgang Weger and Jane Worthington and Rachid Tazi-Ahnini and Nestle, {Frank O} and Adrian Hayday and Per Hoffmann and Juliane Winkelmann and Cisca Wijmenga and Cordelia Langford and Sarah Edkins and Robert Andrews and Hannah Blackburn and Amy Strange and Gavin Band and Pearson, {Richard D} and Damjan Vukcevic and Spencer, {Chris C A} and Alexandros Onoufriadis and Weale, {Michael E} and Campbell, {Linda E} and Mathew, {Christopher G} and Robert Plomin and Viswanathan, {Ananth C} and Emma Gray and Paul Weston and Barker, {Jonathan N W N} and Trembath, {Richard C} and {Collaborative Association Study of Psoriasis (CASP)}",

year = "2012",

month = dec,

doi = "10.1038/ng.2467",

language = "English",

volume = "44",

pages = "1341--1348",

journal = "Nature Genetics",

issn = "1546-1718",

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Tsoi, LC, Spain, SL , Knight, J, Ellinghaus, E, Stuart, PE, Capon, F, Ding, J, Li, Y, Tejasvi, T, Gudjonsson, JE, Kang, HM, Allen, MH, McManus, R, Novelli, G, Samuelsson, L, Schalkwijk, J, Ståhle, M, Burden, AD, Smith, CH, Cork, MJ, Estivill, X, Bowcock, AM, Krueger, GG, Weger, W, Worthington, J, Tazi-Ahnini, R, Nestle, FO , Hayday, A, Hoffmann, P, Winkelmann, J, Wijmenga, C, Langford, C, Edkins, S, Andrews, R, Blackburn, H, Strange, A, Band, G, Pearson, RD, Vukcevic, D, Spencer, CCA, Onoufriadis, A , Weale, ME , Campbell, LE , Mathew, CG , Plomin, R , Viswanathan, AC , Gray, E , Weston, P , Barker, JNWN , Trembath, RC & Collaborative Association Study of Psoriasis (CASP) 2012, 'Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity', Nature Genetics, vol. 44, no. 12, pp. 1341-1348. https://doi.org/10.1038/ng.2467

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T1 - Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity

AU - Tsoi, Lam C

AU - Spain, Sarah L

AU - Knight, Jo

AU - Ellinghaus, Eva

AU - Stuart, Philip E

AU - Capon, Francesca

AU - Ding, Jun

AU - Li, Yanming

AU - Tejasvi, Trilokraj

AU - Gudjonsson, Johann E

AU - Kang, Hyun M

AU - Allen, Michael H

AU - McManus, Ross

AU - Novelli, Giuseppe

AU - Samuelsson, Lena

AU - Schalkwijk, Joost

AU - Ståhle, Mona

AU - Burden, A David

AU - Smith, Catherine H

AU - Cork, Michael J

AU - Estivill, Xavier

AU - Bowcock, Anne M

AU - Krueger, Gerald G

AU - Weger, Wolfgang

AU - Worthington, Jane

AU - Tazi-Ahnini, Rachid

AU - Nestle, Frank O

AU - Hayday, Adrian

AU - Hoffmann, Per

AU - Winkelmann, Juliane

AU - Wijmenga, Cisca

AU - Langford, Cordelia

AU - Edkins, Sarah

AU - Andrews, Robert

AU - Blackburn, Hannah

AU - Strange, Amy

AU - Band, Gavin

AU - Pearson, Richard D

AU - Vukcevic, Damjan

AU - Spencer, Chris C A

AU - Onoufriadis, Alexandros

AU - Weale, Michael E

AU - Campbell, Linda E

AU - Mathew, Christopher G

AU - Plomin, Robert

AU - Viswanathan, Ananth C

AU - Gray, Emma

AU - Weston, Paul

AU - Barker, Jonathan N W N

AU - Trembath, Richard C

AU - Collaborative Association Study of Psoriasis (CASP)

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N2 - To gain further insight into the genetic architecture of psoriasis, we conducted a meta-analysis of 3 genome-wide association studies (GWAS) and 2 independent data sets genotyped on the Immunochip, including 10,588 cases and 22,806 controls. We identified 15 new susceptibility loci, increasing to 36 the number associated with psoriasis in European individuals. We also identified, using conditional analyses, five independent signals within previously known loci. The newly identified loci shared with other autoimmune diseases include candidate genes with roles in regulating T-cell function (such as RUNX3, TAGAP and STAT3). Notably, they included candidate genes whose products are involved in innate host defense, including interferon-mediated antiviral responses (DDX58), macrophage activation (ZC3H12C) and nuclear factor (NF)-κB signaling (CARD14 and CARM1). These results portend a better understanding of shared and distinctive genetic determinants of immune-mediated inflammatory disorders and emphasize the importance of the skin in innate and acquired host defense.

AB - To gain further insight into the genetic architecture of psoriasis, we conducted a meta-analysis of 3 genome-wide association studies (GWAS) and 2 independent data sets genotyped on the Immunochip, including 10,588 cases and 22,806 controls. We identified 15 new susceptibility loci, increasing to 36 the number associated with psoriasis in European individuals. We also identified, using conditional analyses, five independent signals within previously known loci. The newly identified loci shared with other autoimmune diseases include candidate genes with roles in regulating T-cell function (such as RUNX3, TAGAP and STAT3). Notably, they included candidate genes whose products are involved in innate host defense, including interferon-mediated antiviral responses (DDX58), macrophage activation (ZC3H12C) and nuclear factor (NF)-κB signaling (CARD14 and CARM1). These results portend a better understanding of shared and distinctive genetic determinants of immune-mediated inflammatory disorders and emphasize the importance of the skin in innate and acquired host defense.

U2 - 10.1038/ng.2467

DO - 10.1038/ng.2467

M3 - Article

C2 - 23143594

SN - 1546-1718

VL - 44

SP - 1341

EP - 1348

JO - Nature Genetics

JF - Nature Genetics

IS - 12

ER -

Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity

Abstract

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