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

Richard Trembath and colleagues report a meta-analysis of genome-wide association studies for psoriasis, including 2 cohorts genotyped on the custom Immunochip array, in a total of 10,588 cases and 22,806 controls. They identify 15 new susceptibility loci and refine signals in previously known loci,...

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Veröffentlicht in:Nature genetics 2012-12, Vol.44 (12), p.1341-1348
Hauptverfasser: Tsoi, Lam C, Spain, Sarah L, Knight, Jo, Ellinghaus, Eva, Stuart, Philip E, Capon, Francesca, Ding, Jun, Li, Yanming, Tejasvi, Trilokraj, Gudjonsson, Johann E, Kang, Hyun M, Allen, Michael H, McManus, Ross, Novelli, Giuseppe, Samuelsson, Lena, Schalkwijk, Joost, Ståhle, Mona, Burden, A David, Smith, Catherine H, Cork, Michael J, Estivill, Xavier, Bowcock, Anne M, Krueger, Gerald G, Weger, Wolfgang, Worthington, Jane, Tazi-Ahnini, Rachid, Nestle, Frank O, Hayday, Adrian, Hoffmann, Per, Winkelmann, Juliane, Wijmenga, Cisca, Langford, Cordelia, Edkins, Sarah, Andrews, Robert, Blackburn, Hannah, Strange, Amy, Band, Gavin, Pearson, Richard D, Vukcevic, Damjan, Spencer, Chris C A, Deloukas, Panos, Mrowietz, Ulrich, Schreiber, Stefan, Weidinger, Stephan, Koks, Sulev, Kingo, Külli, Esko, Tonu, Metspalu, Andres, Lim, Henry W, Voorhees, John J, Weichenthal, Michael, Wichmann, H Erich, Chandran, Vinod, Rosen, Cheryl F, Rahman, Proton, Gladman, Dafna D, Griffiths, Christopher E M, Reis, Andre, Kere, Juha, Nair, Rajan P, Franke, Andre, Barker, Jonathan N W N, Abecasis, Goncalo R, Elder, James T, Trembath, Richard C
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container_issue 12
container_start_page 1341
container_title Nature genetics
container_volume 44
creator Tsoi, Lam C
Spain, Sarah L
Knight, Jo
Ellinghaus, Eva
Stuart, Philip E
Capon, Francesca
Ding, Jun
Li, Yanming
Tejasvi, Trilokraj
Gudjonsson, Johann E
Kang, Hyun M
Allen, Michael H
McManus, Ross
Novelli, Giuseppe
Samuelsson, Lena
Schalkwijk, Joost
Ståhle, Mona
Burden, A David
Smith, Catherine H
Cork, Michael J
Estivill, Xavier
Bowcock, Anne M
Krueger, Gerald G
Weger, Wolfgang
Worthington, Jane
Tazi-Ahnini, Rachid
Nestle, Frank O
Hayday, Adrian
Hoffmann, Per
Winkelmann, Juliane
Wijmenga, Cisca
Langford, Cordelia
Edkins, Sarah
Andrews, Robert
Blackburn, Hannah
Strange, Amy
Band, Gavin
Pearson, Richard D
Vukcevic, Damjan
Spencer, Chris C A
Deloukas, Panos
Mrowietz, Ulrich
Schreiber, Stefan
Weidinger, Stephan
Koks, Sulev
Kingo, Külli
Esko, Tonu
Metspalu, Andres
Lim, Henry W
Voorhees, John J
Weichenthal, Michael
Wichmann, H Erich
Chandran, Vinod
Rosen, Cheryl F
Rahman, Proton
Gladman, Dafna D
Griffiths, Christopher E M
Reis, Andre
Kere, Juha
Nair, Rajan P
Franke, Andre
Barker, Jonathan N W N
Abecasis, Goncalo R
Elder, James T
Trembath, Richard C
description Richard Trembath and colleagues report a meta-analysis of genome-wide association studies for psoriasis, including 2 cohorts genotyped on the custom Immunochip array, in a total of 10,588 cases and 22,806 controls. They identify 15 new susceptibility loci and refine signals in previously known loci, highlighting a role for innate host defense in susceptibility to psoriasis. 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.
doi_str_mv 10.1038/ng.2467
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They identify 15 new susceptibility loci and refine signals in previously known loci, highlighting a role for innate host defense in susceptibility to psoriasis. 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.</description><identifier>ISSN: 1061-4036</identifier><identifier>ISSN: 1546-1718</identifier><identifier>EISSN: 1546-1718</identifier><identifier>DOI: 10.1038/ng.2467</identifier><identifier>PMID: 23143594</identifier><identifier>CODEN: NGENEC</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>631/208/205/2138 ; 631/250/249/1313/1758 ; Agriculture ; Animal Genetics and Genomics ; Autoimmune diseases ; Biological and medical sciences ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; CARD Signaling Adaptor Proteins - genetics ; CARD Signaling Adaptor Proteins - immunology ; Chromosomes ; Core Binding Factor Alpha 3 Subunit - genetics ; Core Binding Factor Alpha 3 Subunit - immunology ; DEAD Box Protein 58 ; DEAD-box RNA Helicases - genetics ; DEAD-box RNA Helicases - immunology ; Dermatologi och venereologi ; Dermatology ; Dermatology and Venereal Diseases ; Disease susceptibility ; Fundamental and applied biological sciences. Psychology ; Gene expression ; Gene Function ; genetic analysis ; Genetic aspects ; Genetic Loci ; Genetic Predisposition to Disease ; Genetics of eukaryotes. Biological and molecular evolution ; Genome-Wide Association Study ; GTPase-Activating Proteins - genetics ; GTPase-Activating Proteins - immunology ; Guanylate Cyclase - genetics ; Guanylate Cyclase - immunology ; Human Genetics ; Humans ; Immunity, Innate - genetics ; innate immunity ; letter ; Medical sciences ; Membrane Proteins - genetics ; Membrane Proteins - immunology ; Oligonucleotide Array Sequence Analysis ; Physiological aspects ; Polymorphism, Single Nucleotide ; Psoriasis ; Psoriasis - genetics ; Psoriasis - immunology ; Psoriasis. Parapsoriasis. Lichen ; Receptors, Immunologic ; Risk factors ; Skin - immunology ; STAT3 Transcription Factor - genetics ; STAT3 Transcription Factor - immunology ; T-Lymphocytes - immunology ; White People - genetics</subject><ispartof>Nature genetics, 2012-12, Vol.44 (12), p.1341-1348</ispartof><rights>Springer Nature America, Inc. 2012</rights><rights>2014 INIST-CNRS</rights><rights>COPYRIGHT 2012 Nature Publishing 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Giuseppe</creatorcontrib><creatorcontrib>Samuelsson, Lena</creatorcontrib><creatorcontrib>Schalkwijk, Joost</creatorcontrib><creatorcontrib>Ståhle, Mona</creatorcontrib><creatorcontrib>Burden, A David</creatorcontrib><creatorcontrib>Smith, Catherine H</creatorcontrib><creatorcontrib>Cork, Michael J</creatorcontrib><creatorcontrib>Estivill, Xavier</creatorcontrib><creatorcontrib>Bowcock, Anne M</creatorcontrib><creatorcontrib>Krueger, Gerald G</creatorcontrib><creatorcontrib>Weger, Wolfgang</creatorcontrib><creatorcontrib>Worthington, Jane</creatorcontrib><creatorcontrib>Tazi-Ahnini, Rachid</creatorcontrib><creatorcontrib>Nestle, Frank O</creatorcontrib><creatorcontrib>Hayday, Adrian</creatorcontrib><creatorcontrib>Hoffmann, Per</creatorcontrib><creatorcontrib>Winkelmann, Juliane</creatorcontrib><creatorcontrib>Wijmenga, Cisca</creatorcontrib><creatorcontrib>Langford, Cordelia</creatorcontrib><creatorcontrib>Edkins, Sarah</creatorcontrib><creatorcontrib>Andrews, Robert</creatorcontrib><creatorcontrib>Blackburn, Hannah</creatorcontrib><creatorcontrib>Strange, Amy</creatorcontrib><creatorcontrib>Band, Gavin</creatorcontrib><creatorcontrib>Pearson, Richard D</creatorcontrib><creatorcontrib>Vukcevic, Damjan</creatorcontrib><creatorcontrib>Spencer, Chris C A</creatorcontrib><creatorcontrib>Deloukas, Panos</creatorcontrib><creatorcontrib>Mrowietz, Ulrich</creatorcontrib><creatorcontrib>Schreiber, Stefan</creatorcontrib><creatorcontrib>Weidinger, Stephan</creatorcontrib><creatorcontrib>Koks, Sulev</creatorcontrib><creatorcontrib>Kingo, Külli</creatorcontrib><creatorcontrib>Esko, Tonu</creatorcontrib><creatorcontrib>Metspalu, Andres</creatorcontrib><creatorcontrib>Lim, Henry W</creatorcontrib><creatorcontrib>Voorhees, John J</creatorcontrib><creatorcontrib>Weichenthal, Michael</creatorcontrib><creatorcontrib>Wichmann, H Erich</creatorcontrib><creatorcontrib>Chandran, Vinod</creatorcontrib><creatorcontrib>Rosen, Cheryl F</creatorcontrib><creatorcontrib>Rahman, Proton</creatorcontrib><creatorcontrib>Gladman, Dafna D</creatorcontrib><creatorcontrib>Griffiths, Christopher E M</creatorcontrib><creatorcontrib>Reis, Andre</creatorcontrib><creatorcontrib>Kere, Juha</creatorcontrib><creatorcontrib>Nair, Rajan P</creatorcontrib><creatorcontrib>Franke, Andre</creatorcontrib><creatorcontrib>Barker, Jonathan N W N</creatorcontrib><creatorcontrib>Abecasis, Goncalo R</creatorcontrib><creatorcontrib>Elder, James T</creatorcontrib><creatorcontrib>Trembath, Richard C</creatorcontrib><creatorcontrib>Psoriasis Association Genetics Extension</creatorcontrib><creatorcontrib>Genetic Analysis of Psoriasis Consortium</creatorcontrib><creatorcontrib>Collaborative Association Study of Psoriasis (CASP)</creatorcontrib><creatorcontrib>Wellcome Trust Case Control Consortium 2</creatorcontrib><title>Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity</title><title>Nature genetics</title><addtitle>Nat Genet</addtitle><addtitle>Nat Genet</addtitle><description>Richard Trembath and colleagues report a meta-analysis of genome-wide association studies for psoriasis, including 2 cohorts genotyped on the custom Immunochip array, in a total of 10,588 cases and 22,806 controls. They identify 15 new susceptibility loci and refine signals in previously known loci, highlighting a role for innate host defense in susceptibility to psoriasis. 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.</description><subject>631/208/205/2138</subject><subject>631/250/249/1313/1758</subject><subject>Agriculture</subject><subject>Animal Genetics and Genomics</subject><subject>Autoimmune diseases</subject><subject>Biological and medical sciences</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>CARD Signaling Adaptor Proteins - genetics</subject><subject>CARD Signaling Adaptor Proteins - immunology</subject><subject>Chromosomes</subject><subject>Core Binding Factor Alpha 3 Subunit - genetics</subject><subject>Core Binding Factor Alpha 3 Subunit - immunology</subject><subject>DEAD Box Protein 58</subject><subject>DEAD-box RNA Helicases - genetics</subject><subject>DEAD-box RNA Helicases - immunology</subject><subject>Dermatologi och venereologi</subject><subject>Dermatology</subject><subject>Dermatology and Venereal Diseases</subject><subject>Disease susceptibility</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene expression</subject><subject>Gene Function</subject><subject>genetic analysis</subject><subject>Genetic aspects</subject><subject>Genetic Loci</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetics of eukaryotes. Biological and molecular evolution</subject><subject>Genome-Wide Association Study</subject><subject>GTPase-Activating Proteins - genetics</subject><subject>GTPase-Activating Proteins - immunology</subject><subject>Guanylate Cyclase - genetics</subject><subject>Guanylate Cyclase - immunology</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Immunity, Innate - genetics</subject><subject>innate immunity</subject><subject>letter</subject><subject>Medical sciences</subject><subject>Membrane Proteins - genetics</subject><subject>Membrane Proteins - immunology</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Physiological aspects</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Psoriasis</subject><subject>Psoriasis - genetics</subject><subject>Psoriasis - immunology</subject><subject>Psoriasis. Parapsoriasis. Lichen</subject><subject>Receptors, Immunologic</subject><subject>Risk factors</subject><subject>Skin - immunology</subject><subject>STAT3 Transcription Factor - genetics</subject><subject>STAT3 Transcription Factor - immunology</subject><subject>T-Lymphocytes - immunology</subject><subject>White People - genetics</subject><issn>1061-4036</issn><issn>1546-1718</issn><issn>1546-1718</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>D8T</sourceid><recordid>eNqN0luL1DAUB_Aiiruu4jeQgIj60DEnl6bzuCxeBhYWvL1JSNukk7VNuknKut_elBl3GRSVUhpOf6cl_5yieAp4BZjWb1y_IqwS94pj4KwqQUB9P69xBSXDtDoqHsV4iTEwhuuHxRGhwChfs-Pi26bTLlljW5Wsd8gbBBw5fY2m6INV0UYU59jqKdnGDjbdoMG3Fm1tvx3ynSJKW42CH_TSa51TSSM7jrPL9nHxwKgh6if750nx5d3bz2cfyvOL95uz0_OyFYSnsmFGE86Bdw1nrGtFJTAzWLCGVqAASKUq03GgCjpjgNYVW-d9QiM0Jrjj9KQod9-N13qaGzkFO6pwI72ycl_6nldackoZY3_1_TzJXOrnxYNYGrJ_tfNT8FezjkmONmcyDMppP0eZ02SY8LXg_6aE5A2tCaGZPt_RXg1aWmd8CqpduDylAFSIfJZZrf6g8tXp0bbeaWNz_aDh9UFDNkn_SL2aY5SbTx__3158PbQvd7YNPsagzW1sgOUyhdL1cpnCLJ_tM5ibUXe37tfYZfBiD1Rs1WCCcq2Ndy6fP_Aa7sKM-ZXrdZCXfg4uj9Jv__wJ567uEw</recordid><startdate>20121201</startdate><enddate>20121201</enddate><creator>Tsoi, Lam C</creator><creator>Spain, Sarah L</creator><creator>Knight, Jo</creator><creator>Ellinghaus, Eva</creator><creator>Stuart, Philip E</creator><creator>Capon, Francesca</creator><creator>Ding, Jun</creator><creator>Li, Yanming</creator><creator>Tejasvi, Trilokraj</creator><creator>Gudjonsson, Johann E</creator><creator>Kang, Hyun M</creator><creator>Allen, Michael H</creator><creator>McManus, Ross</creator><creator>Novelli, Giuseppe</creator><creator>Samuelsson, Lena</creator><creator>Schalkwijk, Joost</creator><creator>Ståhle, Mona</creator><creator>Burden, A David</creator><creator>Smith, Catherine H</creator><creator>Cork, Michael J</creator><creator>Estivill, Xavier</creator><creator>Bowcock, Anne M</creator><creator>Krueger, Gerald G</creator><creator>Weger, Wolfgang</creator><creator>Worthington, Jane</creator><creator>Tazi-Ahnini, Rachid</creator><creator>Nestle, Frank O</creator><creator>Hayday, Adrian</creator><creator>Hoffmann, Per</creator><creator>Winkelmann, Juliane</creator><creator>Wijmenga, Cisca</creator><creator>Langford, Cordelia</creator><creator>Edkins, Sarah</creator><creator>Andrews, Robert</creator><creator>Blackburn, Hannah</creator><creator>Strange, Amy</creator><creator>Band, Gavin</creator><creator>Pearson, Richard D</creator><creator>Vukcevic, Damjan</creator><creator>Spencer, Chris C A</creator><creator>Deloukas, Panos</creator><creator>Mrowietz, Ulrich</creator><creator>Schreiber, Stefan</creator><creator>Weidinger, Stephan</creator><creator>Koks, Sulev</creator><creator>Kingo, Külli</creator><creator>Esko, Tonu</creator><creator>Metspalu, Andres</creator><creator>Lim, Henry W</creator><creator>Voorhees, John J</creator><creator>Weichenthal, Michael</creator><creator>Wichmann, H Erich</creator><creator>Chandran, Vinod</creator><creator>Rosen, Cheryl F</creator><creator>Rahman, Proton</creator><creator>Gladman, Dafna D</creator><creator>Griffiths, Christopher E M</creator><creator>Reis, Andre</creator><creator>Kere, Juha</creator><creator>Nair, Rajan P</creator><creator>Franke, Andre</creator><creator>Barker, Jonathan N W N</creator><creator>Abecasis, Goncalo R</creator><creator>Elder, James T</creator><creator>Trembath, Richard C</creator><general>Nature Publishing Group US</general><general>Nature Publishing Group</general><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>7X8</scope><scope>7TM</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>ADTPV</scope><scope>AOWAS</scope><scope>F1U</scope><scope>D8T</scope><scope>ZZAVC</scope></search><sort><creationdate>20121201</creationdate><title>Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity</title><author>Tsoi, Lam C ; Spain, Sarah L ; Knight, Jo ; Ellinghaus, Eva ; Stuart, Philip E ; Capon, Francesca ; Ding, Jun ; Li, Yanming ; Tejasvi, Trilokraj ; Gudjonsson, Johann E ; Kang, Hyun M ; Allen, Michael H ; McManus, Ross ; Novelli, Giuseppe ; Samuelsson, Lena ; Schalkwijk, Joost ; Ståhle, Mona ; Burden, A David ; Smith, Catherine H ; Cork, Michael J ; Estivill, Xavier ; Bowcock, Anne M ; Krueger, Gerald G ; Weger, Wolfgang ; Worthington, Jane ; Tazi-Ahnini, Rachid ; Nestle, Frank O ; Hayday, Adrian ; Hoffmann, Per ; Winkelmann, Juliane ; Wijmenga, Cisca ; Langford, Cordelia ; Edkins, Sarah ; Andrews, Robert ; Blackburn, Hannah ; Strange, Amy ; Band, Gavin ; Pearson, Richard D ; Vukcevic, Damjan ; Spencer, Chris C A ; Deloukas, Panos ; Mrowietz, Ulrich ; Schreiber, Stefan ; Weidinger, Stephan ; Koks, Sulev ; Kingo, Külli ; Esko, Tonu ; Metspalu, Andres ; Lim, Henry W ; Voorhees, John J ; Weichenthal, Michael ; Wichmann, H Erich ; Chandran, Vinod ; Rosen, Cheryl F ; Rahman, Proton ; Gladman, Dafna D ; Griffiths, Christopher E M ; Reis, Andre ; Kere, Juha ; Nair, Rajan P ; Franke, Andre ; Barker, Jonathan N W N ; Abecasis, Goncalo R ; Elder, James T ; Trembath, Richard C</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c725t-b4fe25515db544dc76704f074b361a1126a6fd513a1dff1386491541b7e020d53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>631/208/205/2138</topic><topic>631/250/249/1313/1758</topic><topic>Agriculture</topic><topic>Animal Genetics and Genomics</topic><topic>Autoimmune diseases</topic><topic>Biological and medical sciences</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>CARD Signaling Adaptor Proteins - genetics</topic><topic>CARD Signaling Adaptor Proteins - immunology</topic><topic>Chromosomes</topic><topic>Core Binding Factor Alpha 3 Subunit - genetics</topic><topic>Core Binding Factor Alpha 3 Subunit - immunology</topic><topic>DEAD Box Protein 58</topic><topic>DEAD-box RNA Helicases - genetics</topic><topic>DEAD-box RNA Helicases - immunology</topic><topic>Dermatologi och venereologi</topic><topic>Dermatology</topic><topic>Dermatology and Venereal Diseases</topic><topic>Disease susceptibility</topic><topic>Fundamental and applied biological sciences. 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They identify 15 new susceptibility loci and refine signals in previously known loci, highlighting a role for innate host defense in susceptibility to psoriasis. 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.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>23143594</pmid><doi>10.1038/ng.2467</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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subjects 631/208/205/2138
631/250/249/1313/1758
Agriculture
Animal Genetics and Genomics
Autoimmune diseases
Biological and medical sciences
Biomedical and Life Sciences
Biomedicine
Cancer Research
CARD Signaling Adaptor Proteins - genetics
CARD Signaling Adaptor Proteins - immunology
Chromosomes
Core Binding Factor Alpha 3 Subunit - genetics
Core Binding Factor Alpha 3 Subunit - immunology
DEAD Box Protein 58
DEAD-box RNA Helicases - genetics
DEAD-box RNA Helicases - immunology
Dermatologi och venereologi
Dermatology
Dermatology and Venereal Diseases
Disease susceptibility
Fundamental and applied biological sciences. Psychology
Gene expression
Gene Function
genetic analysis
Genetic aspects
Genetic Loci
Genetic Predisposition to Disease
Genetics of eukaryotes. Biological and molecular evolution
Genome-Wide Association Study
GTPase-Activating Proteins - genetics
GTPase-Activating Proteins - immunology
Guanylate Cyclase - genetics
Guanylate Cyclase - immunology
Human Genetics
Humans
Immunity, Innate - genetics
innate immunity
letter
Medical sciences
Membrane Proteins - genetics
Membrane Proteins - immunology
Oligonucleotide Array Sequence Analysis
Physiological aspects
Polymorphism, Single Nucleotide
Psoriasis
Psoriasis - genetics
Psoriasis - immunology
Psoriasis. Parapsoriasis. Lichen
Receptors, Immunologic
Risk factors
Skin - immunology
STAT3 Transcription Factor - genetics
STAT3 Transcription Factor - immunology
T-Lymphocytes - immunology
White People - genetics
title Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity
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