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Identification of 15 new psoriasis susceptibility loci highlights the role of innate immunity.
Nat. Genet. 44, 1341-1348 (2012)
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.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Genome-wide Association ; T-cell Development ; Gene-expression ; Celiac-disease ; Th17 Differentiation ; Signaling Pathways ; Negative Regulator ; Interferon-gamma ; Common Variants ; Multiple Common
ISSN (print) / ISBN
1061-4036
e-ISSN
1546-1718
Journal
Nature Genetics
Quellenangaben
Volume: 44,
Issue: 12,
Pages: 1341-1348
Publisher
Nature Publishing Group
Publishing Place
New York, NY
Non-patent literature
Publications
Reviewing status
Peer reviewed