Final published version
Research output: Contribution to Journal/Magazine › Letter › peer-review
Research output: Contribution to Journal/Magazine › Letter › peer-review
}
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 - Collaborative Association Study of Psoriasis (CASP)
PY - 2012/12
Y1 - 2012/12
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.
KW - CARD Signaling Adaptor Proteins
KW - Core Binding Factor Alpha 3 Subunit
KW - DEAD-box RNA Helicases
KW - European Continental Ancestry Group
KW - GTPase-Activating Proteins
KW - Genetic Loci
KW - Genetic Predisposition to Disease
KW - Genome-Wide Association Study
KW - Guanylate Cyclase
KW - Humans
KW - Immunity, Innate
KW - Membrane Proteins
KW - Oligonucleotide Array Sequence Analysis
KW - Polymorphism, Single Nucleotide
KW - Psoriasis
KW - STAT3 Transcription Factor
KW - Skin
KW - T-Lymphocytes
U2 - 10.1038/ng.2467
DO - 10.1038/ng.2467
M3 - Letter
C2 - 23143594
VL - 44
SP - 1341
EP - 1348
JO - Nature Genetics
JF - Nature Genetics
SN - 1061-4036
IS - 12
ER -