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; Panos Deloukas; Ulrich Mrowietz; Stefan Schreiber; Stephan Weidinger; Sulev Koks; Külli Kingo; Tonu Esko; Andres Metspalu; Henry W. Lim; John J. Voorhees; Michael Weichenthal; H. Erich Wichmann; Vinod Chandran; Cheryl F. Rosen; Proton Rahman; Dafna D. Gladman; Christopher E M Griffiths; Andre Reis; Juha Kere; Rajan P. Nnair; Andre Franke; Jonathan Nn Barker; Ggoncalo R. Abecasis; James Tt Eelder; Richard Ttrembath; Kristina Callis Duffin; Cindy Helms; David Goldgar; Yun Li; Justin Paschall; Mary J. Malloy; Clive R. Pullinger; John P. Kane; Jennifer Gardner; Amy Perlmutter; Andrew Miner; Bing Jian Feng; Ravi Hiremagalore; Robert W. Ike; Enno Christophers; Tilo Henseler; Andreas Ruether; Steven J. Schrodi; Sampath Prahalad; Stephen L. Guthery; Judith Fischer; Wilson Liao; Pui Kwok; Alan Menter; G. Mark Lathrop; C. Wise; Ann B. Begovich; Alexandros Onoufriadis; Michael E. Weale; Angelika Hofer; Wolfgang Salmhofer; Peter Wolf; Kati Kainu; Ulpu Saarialho-Kere; Sari Suomela; Petra Badorf; Ulrike Hüffmeier; Werner Kurrat; Wolfgang Küster; Jesús Lascorz; Rotraut Mössner; Funda Schürmeier-Horst; Markward Ständer; Heiko Traupe; Judith G M Bergboer; Martin Den Heijer; Peter C. Van De Kerkhof; Patrick L J M Zeeuwen; Louise Barnes; Linda E. Campbell; Caitriona Cusack; Ciara Coleman; Judith Conroy; Sean Ennis; Oliver Fitzgerald; Phil Gallagher; Alan D. Irvine; Brian Kirby; Trevor Markham; W. H Irwin McLean; Joe McPartlin; Sarah F. Rogers; Anthony W. Ryan; Agnieszka Zawirska; Emiliano Giardina; Tiziana Lepre; Carlo Perricone; Gemma Martín-Ezquerra; Ramon M. Pujol; Eva Riveira-Munoz; Annica Inerot; Åsa T. Naluai; Lotus Mallbris; Katarina Wolk; Joyce Leman; Anne Barton; Richard B. Warren; Helen S. Young; Isis Ricano-Ponce; Gosia Trynka; Fawnda J. Pellett; Andrew Henschel; Marin Aurand; Bruce Bebo; Christian Gieger; Thomas Illig; Susanne Moebus; Karl Heinz Jöckel; Raimund Erbel; Peter Donnelly; Leena Peltonen; Jenefer M. Blackwell; Elvira Bramon; Matthew A. Brown; Juan P. Casas; Aiden Corvin; Nicholas Craddock; Audrey Duncanson; Janusz Jankowski; Hugh S. Markus; Christopher G. Mathew; Mark I. McCarthy; Colin N A Palmer; Robert Plomin; Anna Rautanen; Stephen J. Sawcer; Nilesh Samani; Ananth C. Viswanathan; Nicholas W. Wood; Céline Bellenguez; Colin Freeman; Garrett Hellenthal; Eleni Giannoulatou; Matti Pirinen; Zhan Su; Sarah E. Hunt; Rhian Gwilliam; Suzannah J. Bumpstead; Serge Dronov; Matthew Gillman; Emma Gray; Naomi Hammond; Alagurevathi Jayakumar; Owen T. McCann; Jennifer Liddle; Marc L. Perez; Simon C. Potter; Radhi Ravindrarajah; Michelle Ricketts; Matthew Waller; Paul Weston; Sara Widaa; Pamela Whittaker; Rajan P. Neir; Jonathan N W N Barker; Goncalo R. Abecasis; James T. Elder; Richard C. Trembath

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, Panos Deloukas, Ulrich Mrowietz, Stefan Schreiber, Stephan Weidinger, Sulev Koks, Külli Kingo, Tonu Esko, Andres Metspalu, Henry W. Lim, John J. Voorhees, Michael Weichenthal, H. Erich Wichmann, Vinod Chandran, Cheryl F. Rosen, Proton Rahman, Dafna D. Gladman, Christopher E M Griffiths, Andre Reis, Juha Kere, Rajan P. Nnair, Andre Franke, Jonathan Nn Barker, Ggoncalo R. Abecasis, James Tt Eelder, Richard Ttrembath, Kristina Callis Duffin, Cindy Helms, David Goldgar, Yun Li, Justin Paschall, Mary J. Malloy, Clive R. Pullinger, John P. Kane, Jennifer Gardner, Amy Perlmutter, Andrew Miner, Bing Jian Feng, Ravi Hiremagalore, Robert W. Ike, Enno Christophers, Tilo Henseler, Andreas Ruether, Steven J. Schrodi, Sampath Prahalad, Stephen L. Guthery, Judith Fischer, Wilson Liao, Pui Kwok, Alan Menter, G. Mark Lathrop, C. Wise, Ann B. Begovich, Alexandros Onoufriadis, Michael E. Weale, Angelika Hofer, Wolfgang Salmhofer, Peter Wolf, Kati Kainu, Ulpu Saarialho-Kere, Sari Suomela, Petra Badorf, Ulrike Hüffmeier, Werner Kurrat, Wolfgang Küster, Jesús Lascorz, Rotraut Mössner, Funda Schürmeier-Horst, Markward Ständer, Heiko Traupe, Judith G M Bergboer, Martin Den Heijer, Peter C. Van De Kerkhof, Patrick L J M Zeeuwen, Louise Barnes, Linda E. Campbell, Caitriona Cusack, Ciara Coleman, Judith Conroy, Sean Ennis, Oliver Fitzgerald, Phil Gallagher, Alan D. Irvine, Brian Kirby, Trevor Markham, W. H Irwin McLean, Joe McPartlin, Sarah F. Rogers, Anthony W. Ryan, Agnieszka Zawirska, Emiliano Giardina, Tiziana Lepre, Carlo Perricone, Gemma Martín-Ezquerra, Ramon M. Pujol, Eva Riveira-Munoz, Annica Inerot, Åsa T. Naluai, Lotus Mallbris, Katarina Wolk, Joyce Leman, Anne Barton, Richard B. Warren, Helen S. Young, Isis Ricano-Ponce, Gosia Trynka, Fawnda J. Pellett, Andrew Henschel, Marin Aurand, Bruce Bebo, Christian Gieger, Thomas Illig, Susanne Moebus, Karl Heinz Jöckel, Raimund Erbel, Peter Donnelly, Leena Peltonen, Jenefer M. Blackwell, Elvira Bramon, Matthew A. Brown, Juan P. Casas, Aiden Corvin, Nicholas Craddock, Audrey Duncanson, Janusz Jankowski, Hugh S. Markus, Christopher G. Mathew, Mark I. McCarthy, Colin N A Palmer, Robert Plomin, Anna Rautanen, Stephen J. Sawcer, Nilesh Samani, Ananth C. Viswanathan, Nicholas W. Wood, Céline Bellenguez, Colin Freeman, Garrett Hellenthal, Eleni Giannoulatou, Matti Pirinen, Zhan Su, Sarah E. Hunt, Rhian Gwilliam, Suzannah J. Bumpstead, Serge Dronov, Matthew Gillman, Emma Gray, Naomi Hammond, Alagurevathi Jayakumar, Owen T. McCann, Jennifer Liddle, Marc L. Perez, Simon C. Potter, Radhi Ravindrarajah, Michelle Ricketts, Matthew Waller, Paul Weston, Sara Widaa, Pamela Whittaker, Rajan P. Neir, Jonathan N W N Barker, Goncalo R. Abecasis, James T. Elder, Richard C. Trembath

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

767 Scopus citations

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 (US)
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
State	Published - Dec 1 2012

ASJC Scopus subject areas

Genetics

Access to Document

10.1038/ng.2467

Cite this

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., ... Trembath, R. C. (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

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, Deloukas, P, Mrowietz, U, Schreiber, S, Weidinger, S, Koks, S, Kingo, K, Esko, T, Metspalu, A, Lim, HW, Voorhees, JJ, Weichenthal, M, Wichmann, HE, Chandran, V, Rosen, CF, Rahman, P, Gladman, DD, Griffiths, CEM, Reis, A, Kere, J, Nnair, RP, Franke, A, Barker, JN, Abecasis, GR, Eelder, JT, Ttrembath, R, Duffin, KC, Helms, C, Goldgar, D, Li, Y, Paschall, J, Malloy, MJ, Pullinger, CR, Kane, JP, Gardner, J, Perlmutter, A, Miner, A, Feng, BJ, Hiremagalore, R, Ike, RW, Christophers, E, Henseler, T, Ruether, A, Schrodi, SJ, Prahalad, S, Guthery, SL, Fischer, J, Liao, W, Kwok, P, Menter, A, Lathrop, GM, Wise, C, Begovich, AB, Onoufriadis, A, Weale, ME, Hofer, A, Salmhofer, W, Wolf, P, Kainu, K, Saarialho-Kere, U, Suomela, S, Badorf, P, Hüffmeier, U, Kurrat, W, Küster, W, Lascorz, J, Mössner, R, Schürmeier-Horst, F, Ständer, M, Traupe, H, Bergboer, JGM, Heijer, MD, Van De Kerkhof, PC, Zeeuwen, PLJM, Barnes, L, Campbell, LE, Cusack, C, Coleman, C, Conroy, J, Ennis, S, Fitzgerald, O, Gallagher, P, Irvine, AD, Kirby, B, Markham, T, McLean, WHI, McPartlin, J, Rogers, SF, Ryan, AW, Zawirska, A, Giardina, E, Lepre, T, Perricone, C, Martín-Ezquerra, G, Pujol, RM, Riveira-Munoz, E, Inerot, A, Naluai, ÅT, Mallbris, L, Wolk, K, Leman, J, Barton, A, Warren, RB, Young, HS, Ricano-Ponce, I, Trynka, G, Pellett, FJ, Henschel, A, Aurand, M, Bebo, B, Gieger, C, Illig, T, Moebus, S, Jöckel, KH, Erbel, R, Donnelly, P, Peltonen, L, Blackwell, JM, Bramon, E, Brown, MA, Casas, JP, Corvin, A, Craddock, N, Duncanson, A, Jankowski, J, Markus, HS, Mathew, CG, McCarthy, MI, Palmer, CNA, Plomin, R, Rautanen, A, Sawcer, SJ, Samani, N, Viswanathan, AC, Wood, NW, Bellenguez, C, Freeman, C, Hellenthal, G, Giannoulatou, E, Pirinen, M, Su, Z, Hunt, SE, Gwilliam, R, Bumpstead, SJ, Dronov, S, Gillman, M, Gray, E, Hammond, N, Jayakumar, A, McCann, OT, Liddle, J, Perez, ML, Potter, SC, Ravindrarajah, R, Ricketts, M, Waller, M, Weston, P, Widaa, S, Whittaker, P, Neir, RP, Barker, JNWN, Abecasis, GR, Elder, JT & Trembath, RC 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

@article{7e7ba1410170469aaf53f15a98d252d2,

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 Panos Deloukas and Ulrich Mrowietz and Stefan Schreiber and Stephan Weidinger and Sulev Koks and K{\"u}lli Kingo and Tonu Esko and Andres Metspalu and Lim, {Henry W.} and Voorhees, {John J.} and Michael Weichenthal and Wichmann, {H. Erich} and Vinod Chandran and Rosen, {Cheryl F.} and Proton Rahman and Gladman, {Dafna D.} and Griffiths, {Christopher E M} and Andre Reis and Juha Kere and Nnair, {Rajan P.} and Andre Franke and Barker, {Jonathan Nn} and Abecasis, {Ggoncalo R.} and Eelder, {James Tt} and Richard Ttrembath and Duffin, {Kristina Callis} and Cindy Helms and David Goldgar and Yun Li and Justin Paschall and Malloy, {Mary J.} and Pullinger, {Clive R.} and Kane, {John P.} and Jennifer Gardner and Amy Perlmutter and Andrew Miner and Feng, {Bing Jian} and Ravi Hiremagalore and Ike, {Robert W.} and Enno Christophers and Tilo Henseler and Andreas Ruether and Schrodi, {Steven J.} and Sampath Prahalad and Guthery, {Stephen L.} and Judith Fischer and Wilson Liao and Pui Kwok and Alan Menter and Lathrop, {G. Mark} and C. Wise and Begovich, {Ann B.} and Alexandros Onoufriadis and Weale, {Michael E.} and Angelika Hofer and Wolfgang Salmhofer and Peter Wolf and Kati Kainu and Ulpu Saarialho-Kere and Sari Suomela and Petra Badorf and Ulrike H{\"u}ffmeier and Werner Kurrat and Wolfgang K{\"u}ster and Jes{\'u}s Lascorz and Rotraut M{\"o}ssner and Funda Sch{\"u}rmeier-Horst and Markward St{\"a}nder and Heiko Traupe and Bergboer, {Judith G M} and Heijer, {Martin Den} and {Van De Kerkhof}, {Peter C.} and Zeeuwen, {Patrick L J M} and Louise Barnes and Campbell, {Linda E.} and Caitriona Cusack and Ciara Coleman and Judith Conroy and Sean Ennis and Oliver Fitzgerald and Phil Gallagher and Irvine, {Alan D.} and Brian Kirby and Trevor Markham and McLean, {W. H Irwin} and Joe McPartlin and Rogers, {Sarah F.} and Ryan, {Anthony W.} and Agnieszka Zawirska and Emiliano Giardina and Tiziana Lepre and Carlo Perricone and Gemma Mart{\'i}n-Ezquerra and Pujol, {Ramon M.} and Eva Riveira-Munoz and Annica Inerot and Naluai, {{\AA}sa T.} and Lotus Mallbris and Katarina Wolk and Joyce Leman and Anne Barton and Warren, {Richard B.} and Young, {Helen S.} and Isis Ricano-Ponce and Gosia Trynka and Pellett, {Fawnda J.} and Andrew Henschel and Marin Aurand and Bruce Bebo and Christian Gieger and Thomas Illig and Susanne Moebus and J{\"o}ckel, {Karl Heinz} and Raimund Erbel and Peter Donnelly and Leena Peltonen and Blackwell, {Jenefer M.} and Elvira Bramon and Brown, {Matthew A.} and Casas, {Juan P.} and Aiden Corvin and Nicholas Craddock and Audrey Duncanson and Janusz Jankowski and Markus, {Hugh S.} and Mathew, {Christopher G.} and McCarthy, {Mark I.} and Palmer, {Colin N A} and Robert Plomin and Anna Rautanen and Sawcer, {Stephen J.} and Nilesh Samani and Viswanathan, {Ananth C.} and Wood, {Nicholas W.} and C{\'e}line Bellenguez and Colin Freeman and Garrett Hellenthal and Eleni Giannoulatou and Matti Pirinen and Zhan Su and Hunt, {Sarah E.} and Rhian Gwilliam and Bumpstead, {Suzannah J.} and Serge Dronov and Matthew Gillman and Emma Gray and Naomi Hammond and Alagurevathi Jayakumar and McCann, {Owen T.} and Jennifer Liddle and Perez, {Marc L.} and Potter, {Simon C.} and Radhi Ravindrarajah and Michelle Ricketts and Matthew Waller and Paul Weston and Sara Widaa and Pamela Whittaker and Neir, {Rajan P.} and Barker, {Jonathan N W N} and Abecasis, {Goncalo R.} and Elder, {James T.} and Trembath, {Richard C.}",

note = "Funding Information: Major support for this study was provided by the US National Institutes of Health, the Wellcome Trust and the German Research Foundation. We thank J.C. Barrett for contribution to the design of the Immunochip and helpful analytical discussion, as well as E. Gray, S. Bumpstead, D. Simpkin and the staff of the Wellcome Trust Sanger Institute Sample Management and Genotyping teams for their genotyping and analytical contributions. We acknowledge use of the British 1958 Birth Cohort DNA collection, funded by the UK Medical Research Council (G0000934) and the Funding Information: Wellcome Trust (068545/Z/02), and the UK National Blood Service controls, funded by the Wellcome Trust. We acknowledge CASP for the contribution of GWAS data, as well as the provision of control DNA samples by the Cooperative Research in the Region of Augsburg (KORA) and Heinz-Nixdorf Recall (Risk Factors, Evaluation of Coronary Calcification and Lifestyle) study (HNR) and genotyping data generated by the Dietary, Lifestyle and Genetic determinants of Obesity and Metabolic syndrome (DILGOM) Consortium. We thank the Barbara and Neal Henschel Charitable Foundation for their support of the National Psoriasis Victor Henschel BioBank. We acknowledge the Genetic repository in Ireland for Psoriasis and Psoriatic Arthritis (GRIPPsA), the Irish blood transfusion service/Trinity College Dublin Biobank and the Dublin Centre for Clinical Research (funded by the Health Research Board and the Wellcome Trust). A detailed list of contributing consortia and relevant funding support is provided in the Supplementary Note.",

year = "2012",

month = dec,

day = "1",

doi = "10.1038/ng.2467",

language = "English (US)",

volume = "44",

pages = "1341--1348",

journal = "Nature genetics",

issn = "1061-4036",

publisher = "Nature Publishing Group",

number = "12",

}

TY - JOUR

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 - Deloukas, Panos

AU - Mrowietz, Ulrich

AU - Schreiber, Stefan

AU - Weidinger, Stephan

AU - Koks, Sulev

AU - Kingo, Külli

AU - Esko, Tonu

AU - Metspalu, Andres

AU - Lim, Henry W.

AU - Voorhees, John J.

AU - Weichenthal, Michael

AU - Wichmann, H. Erich

AU - Chandran, Vinod

AU - Rosen, Cheryl F.

AU - Rahman, Proton

AU - Gladman, Dafna D.

AU - Griffiths, Christopher E M

AU - Reis, Andre

AU - Kere, Juha

AU - Nnair, Rajan P.

AU - Franke, Andre

AU - Barker, Jonathan Nn

AU - Abecasis, Ggoncalo R.

AU - Eelder, James Tt

AU - Ttrembath, Richard

AU - Duffin, Kristina Callis

AU - Helms, Cindy

AU - Goldgar, David

AU - Li, Yun

AU - Paschall, Justin

AU - Malloy, Mary J.

AU - Pullinger, Clive R.

AU - Kane, John P.

AU - Gardner, Jennifer

AU - Perlmutter, Amy

AU - Miner, Andrew

AU - Feng, Bing Jian

AU - Hiremagalore, Ravi

AU - Ike, Robert W.

AU - Christophers, Enno

AU - Henseler, Tilo

AU - Ruether, Andreas

AU - Schrodi, Steven J.

AU - Prahalad, Sampath

AU - Guthery, Stephen L.

AU - Fischer, Judith

AU - Liao, Wilson

AU - Kwok, Pui

AU - Menter, Alan

AU - Lathrop, G. Mark

AU - Wise, C.

AU - Begovich, Ann B.

AU - Onoufriadis, Alexandros

AU - Weale, Michael E.

AU - Hofer, Angelika

AU - Salmhofer, Wolfgang

AU - Wolf, Peter

AU - Kainu, Kati

AU - Saarialho-Kere, Ulpu

AU - Suomela, Sari

AU - Badorf, Petra

AU - Hüffmeier, Ulrike

AU - Kurrat, Werner

AU - Küster, Wolfgang

AU - Lascorz, Jesús

AU - Mössner, Rotraut

AU - Schürmeier-Horst, Funda

AU - Ständer, Markward

AU - Traupe, Heiko

AU - Bergboer, Judith G M

AU - Heijer, Martin Den

AU - Van De Kerkhof, Peter C.

AU - Zeeuwen, Patrick L J M

AU - Barnes, Louise

AU - Campbell, Linda E.

AU - Cusack, Caitriona

AU - Coleman, Ciara

AU - Conroy, Judith

AU - Ennis, Sean

AU - Fitzgerald, Oliver

AU - Gallagher, Phil

AU - Irvine, Alan D.

AU - Kirby, Brian

AU - Markham, Trevor

AU - McLean, W. H Irwin

AU - McPartlin, Joe

AU - Rogers, Sarah F.

AU - Ryan, Anthony W.

AU - Zawirska, Agnieszka

AU - Giardina, Emiliano

AU - Lepre, Tiziana

AU - Perricone, Carlo

AU - Martín-Ezquerra, Gemma

AU - Pujol, Ramon M.

AU - Riveira-Munoz, Eva

AU - Inerot, Annica

AU - Naluai, Åsa T.

AU - Mallbris, Lotus

AU - Wolk, Katarina

AU - Leman, Joyce

AU - Barton, Anne

AU - Warren, Richard B.

AU - Young, Helen S.

AU - Ricano-Ponce, Isis

AU - Trynka, Gosia

AU - Pellett, Fawnda J.

AU - Henschel, Andrew

AU - Aurand, Marin

AU - Bebo, Bruce

AU - Gieger, Christian

AU - Illig, Thomas

AU - Moebus, Susanne

AU - Jöckel, Karl Heinz

AU - Erbel, Raimund

AU - Donnelly, Peter

AU - Peltonen, Leena

AU - Blackwell, Jenefer M.

AU - Bramon, Elvira

AU - Brown, Matthew A.

AU - Casas, Juan P.

AU - Corvin, Aiden

AU - Craddock, Nicholas

AU - Duncanson, Audrey

AU - Jankowski, Janusz

AU - Markus, Hugh S.

AU - Mathew, Christopher G.

AU - McCarthy, Mark I.

AU - Palmer, Colin N A

AU - Plomin, Robert

AU - Rautanen, Anna

AU - Sawcer, Stephen J.

AU - Samani, Nilesh

AU - Viswanathan, Ananth C.

AU - Wood, Nicholas W.

AU - Bellenguez, Céline

AU - Freeman, Colin

AU - Hellenthal, Garrett

AU - Giannoulatou, Eleni

AU - Pirinen, Matti

AU - Su, Zhan

AU - Hunt, Sarah E.

AU - Gwilliam, Rhian

AU - Bumpstead, Suzannah J.

AU - Dronov, Serge

AU - Gillman, Matthew

AU - Gray, Emma

AU - Hammond, Naomi

AU - Jayakumar, Alagurevathi

AU - McCann, Owen T.

AU - Liddle, Jennifer

AU - Perez, Marc L.

AU - Potter, Simon C.

AU - Ravindrarajah, Radhi

AU - Ricketts, Michelle

AU - Waller, Matthew

AU - Weston, Paul

AU - Widaa, Sara

AU - Whittaker, Pamela

AU - Neir, Rajan P.

AU - Barker, Jonathan N W N

AU - Abecasis, Goncalo R.

AU - Elder, James T.

AU - Trembath, Richard C.

N1 - Funding Information: Major support for this study was provided by the US National Institutes of Health, the Wellcome Trust and the German Research Foundation. We thank J.C. Barrett for contribution to the design of the Immunochip and helpful analytical discussion, as well as E. Gray, S. Bumpstead, D. Simpkin and the staff of the Wellcome Trust Sanger Institute Sample Management and Genotyping teams for their genotyping and analytical contributions. We acknowledge use of the British 1958 Birth Cohort DNA collection, funded by the UK Medical Research Council (G0000934) and the Funding Information: Wellcome Trust (068545/Z/02), and the UK National Blood Service controls, funded by the Wellcome Trust. We acknowledge CASP for the contribution of GWAS data, as well as the provision of control DNA samples by the Cooperative Research in the Region of Augsburg (KORA) and Heinz-Nixdorf Recall (Risk Factors, Evaluation of Coronary Calcification and Lifestyle) study (HNR) and genotyping data generated by the Dietary, Lifestyle and Genetic determinants of Obesity and Metabolic syndrome (DILGOM) Consortium. We thank the Barbara and Neal Henschel Charitable Foundation for their support of the National Psoriasis Victor Henschel BioBank. We acknowledge the Genetic repository in Ireland for Psoriasis and Psoriatic Arthritis (GRIPPsA), the Irish blood transfusion service/Trinity College Dublin Biobank and the Dublin Centre for Clinical Research (funded by the Health Research Board and the Wellcome Trust). A detailed list of contributing consortia and relevant funding support is provided in the Supplementary Note.

PY - 2012/12/1

Y1 - 2012/12/1

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.

UR - http://www.scopus.com/inward/record.url?scp=84870512735&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84870512735&partnerID=8YFLogxK

U2 - 10.1038/ng.2467

DO - 10.1038/ng.2467

M3 - Article

C2 - 23143594

AN - SCOPUS:84870512735

SN - 1061-4036

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

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