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

被引：785

作者：

Tsoi, Lam C. ^{[2
]}

Spain, Sarah L. ^{[1
]}

Knight, Jo ^{[3
,4
]}

Ellinghaus, Eva ^{[5
]}

Stuart, Philip E. ^{[6
]}

Capon, Francesca ^{[1
]}

Ding, Jun ^{[2
]}

Li, Yanming ^{[2
]}

Tejasvi, Trilokraj ^{[6
]}

Gudjonsson, Johann E. ^{[6
]}

Kang, Hyun M. ^{[2
]}

Allen, Michael H. ^{[1
]}

McManus, Ross ^{[7
,8
]}

Novelli, Giuseppe ^{[9
,10
]}

Samuelsson, Lena ^{[11
]}

Schalkwijk, Joost ^{[12
]}

Stahle, Mona ^{[13
]}

Burden, A. David ^{[14
]}

Smith, Catherine H. ^{[15
]}

Cork, Michael J. ^{[16
]}

Estivill, Xavier ^{[17
,18
,19
]}

Bowcock, Anne M. ^{[20
]}

Krueger, Gerald G. ^{[21
]}

Weger, Wolfgang ^{[22
]}

Worthington, Jane ^{[23
]}

Tazi-Ahnini, Rachid ^{[16
]}

Nestle, Frank O. ^{[1
]}

Hayday, Adrian ^{[24
]}

Hoffmann, Per ^{[25
,26
]}

Winkelmann, Juliane ^{[27
,28
,29
]}

Wijmenga, Cisca ^{[30
,31
]}

Langford, Cordelia ^{[32
]}

Edkins, Sarah ^{[32
]}

Andrews, Robert ^{[32
]}

Blackburn, Hannah ^{[32
]}

Strange, Amy ^{[33
]}

Band, Gavin ^{[33
]}

Pearson, Richard D. ^{[33
]}

Vukcevic, Damjan ^{[33
]}

Spencer, Chris C. A. ^{[33
]}

Deloukas, Panos ^{[32
]}

Mrowietz, Ulrich ^{[34
]}

Schreiber, Stefan ^{[5
,35
]}

Weidinger, Stephan ^{[34
]}

Koks, Sulev ^{[36
,37
]}

Kingo, Kuelli ^{[38
]}

Esko, Tonu ^{[39
]}

Metspalu, Andres ^{[39
]}

Lim, Henry W. ^{[40
]}

Voorhees, John J. ^{[6
]}

机构：

[1] Kings Coll London, Div Genet & Mol Med, London WC2R 2LS, England

[2] Univ Michigan, Dept Biostat, Ctr Stat Genet, Ann Arbor, MI 48109 USA

[3] Ctr Addict & Mental Hlth, Toronto, ON, Canada

[4] Guys & St Thomas Natl Hlth Serv NHS Fdn Trust, Biomed Res Ctr, NIHR, London, England

[5] Univ Kiel, Inst Clin Mol Biol, Kiel, Germany

[6] Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA

[7] St James Hosp, Trinity Coll Dublin, Dept Clin Med, Dublin, Ireland

[8] Trinity Coll Dublin, Inst Mol Med, Dublin, Ireland

[9] Natl Agcy Evaluat Univ & Res Inst ANVUR, Rome, Italy

[10] San Pietro Hosp, Res Ctr, Rome, Italy

[11] Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Dept Med & Clin Genet, Gothenburg, Sweden

[12] Radboud Univ Nijmegen, Med Ctr, Dept Dermatol, NL-6525 ED Nijmegen, Netherlands

[13] Karolinska Inst, Dept Med, Dermatol Unit, Stockholm, Sweden

[14] Univ Glasgow, Western Infirm, Dept Dermatol, Glasgow G11 6NT, Lanark, Scotland

[15] Kings Coll London, St Johns Inst Dermatol, London WC2R 2LS, England

[16] Univ Sheffield, Dept Infect & Immun, Acad Unit Dermatol Res, Sheffield, S Yorkshire, England

[17] CRG, Genes & Dis Programme, Barcelona, Spain

[18] Pompeu Fabra Univ, Hosp Mar, Res Inst, Barcelona, Spain

[19] Publ Hlth & Epidemiol Network Biomed Res Ctr CIBE, Barcelona, Spain

[20] Washington Univ, Sch Med, Dept Genet, Div Human Genet, St Louis, MO 63110 USA

[21] Univ Utah, Dept Dermatol, Salt Lake City, UT USA

[22] Med Univ Graz, Dept Dermatol, Graz, Austria

[23] Univ Manchester, Manchester Acad Hlth Sci Ctr, Arthrit Res UK Epidemiol Unit, Manchester, Lancs, England

[24] Kings Coll London, Div Immunol Infect & Inflammatory Dis, London WC2R 2LS, England

[25] Univ Bonn, Inst Human Genet, Bonn, Germany

[26] Univ Bonn, Dept Genom, Life & Brain Ctr, Bonn, Germany

[27] Tech Univ Munich, Dept Neurol, Munich, Germany

[28] Tech Univ Munich, Inst Human Genet, Munich, Germany

[29] German Res Ctr Environm Hlth, Helmholtz Zentrum Munich, Inst Human Genet, Munich, Germany

[30] Univ Med Ctr Groningen, Dept Genet, NL-9713 AV Groningen, Netherlands

[31] Univ Groningen, Groningen, Netherlands

[32] Wellcome Trust Sanger Inst, Cambridge, England

[33] Wellcome Trust Ctr Human Genet, Oxford, England

[34] Univ Kiel, Dept Dermatol, Univ Hosp, D-2300 Kiel, Germany

[35] Univ Hosp Schleswig Holstein, PopGen Biobank, Kiel, Germany

[36] Univ Tartu, Ctr Translat Med, Dept Physiol, EE-50090 Tartu, Estonia

[37] Univ Tartu, Ctr Translat Genom, EE-50090 Tartu, Estonia

[38] Univ Tartu, Dept Dermatol & Venerol, EE-50090 Tartu, Estonia

[39] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia

[40] Henry Ford Hosp, Dept Dermatol, Detroit, MI 48202 USA

[41] German Res Ctr Environm Hlth, Helmholtz Zentrum Munich, Inst Epidemiol 1, Neuherberg, Germany

[42] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany

[43] Univ Munich, Klinikum Grosshadern, D-8000 Munich, Germany

[44] Univ Toronto, Toronto Western Hosp, Div Rheumatol, Dept Med, Toronto, ON M5T 2S8, Canada

[45] Univ Toronto, Toronto Western Hosp, Div Dermatol, Dept Med, Toronto, ON M5T 2S8, Canada

[46] Mem Univ Newfoundland, Dept Med, St John, NF, Canada

[47] Univ Manchester, Salford Royal NHS Fdn Trust, Manchester Acad Hlth Sci Ctr, Manchester, Lancs, England

[48] Univ Erlangen Nurnberg, Inst Human Genet, D-91054 Erlangen, Germany

[49] Karolinska Inst, Dept Biosci & Nutr, Stockholm, Sweden

[50] Folkhalsan Inst Genet, Helsinki, Finland

来源：

NATURE GENETICS | 2012年 / 44卷 / 12期

基金：

英国医学研究理事会; 英国惠康基金;

关键词：

GENOME-WIDE ASSOCIATION; T-CELL DEVELOPMENT; SIGNALING PATHWAYS; NEGATIVE REGULATOR; INTERFERON-GAMMA; COMMON VARIANTS; MULTIPLE COMMON; GENE-EXPRESSION; INDUCIBLE GENE; DISEASE;

D O I：

10.1038/ng.2467

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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, TA GAP 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)-kappa B 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.

引用

页码：1341 / 1348

页数：8

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