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Meta-Analysis
. 2015 May 5:6:7001.
doi: 10.1038/ncomms8001.

Enhanced meta-analysis and replication studies identify five new psoriasis susceptibility loci

Lam C Tsoi  1 , Sarah L Spain  2   3 , Eva Ellinghaus  4 , Philip E Stuart  5 , Francesca Capon  2 , Jo Knight  6   7 , Trilokraj Tejasvi  5 , Hyun M Kang  1 , Michael H Allen  2 , Sylviane Lambert  5 , Stefan W Stoll  5 , Stephan Weidinger  8 , Johann E Gudjonsson  5 , Sulev Koks  9 , Külli Kingo  10 , Tonu Esko  11 , Sayantan Das  1 , Andres Metspalu  11 , Michael Weichenthal  8 , Charlotta Enerback  12 , Gerald G Krueger  13 , John J Voorhees  5 , Vinod Chandran  14 , Cheryl F Rosen  15 , Proton Rahman  16 , Dafna D Gladman  14 , Andre Reis  17 , Rajan P Nair  5 , Andre Franke  4 , Jonathan N W N Barker  2 , Goncalo R Abecasis  1 , Richard C Trembath  18 , James T Elder  5   19
Affiliations
Meta-Analysis

Enhanced meta-analysis and replication studies identify five new psoriasis susceptibility loci

Lam C Tsoi et al. Nat Commun. .

Abstract

Psoriasis is a chronic autoimmune disease with complex genetic architecture. Previous genome-wide association studies (GWAS) and a recent meta-analysis using Immunochip data have uncovered 36 susceptibility loci. Here, we extend our previous meta-analysis of European ancestry by refined genotype calling and imputation and by the addition of 5,033 cases and 5,707 controls. The combined analysis, consisting of over 15,000 cases and 27,000 controls, identifies five new psoriasis susceptibility loci at genome-wide significance (P<5 × 10(-8)). The newly identified signals include two that reside in intergenic regions (1q31.1 and 5p13.1) and three residing near PLCL2 (3p24.3), NFKBIZ (3q12.3) and CAMK2G (10q22.2). We further demonstrate that NFKBIZ is a TRAF3IP2-dependent target of IL-17 signalling in human skin keratinocytes, thereby functionally linking two strong candidate genes. These results further integrate the genetics and immunology of psoriasis, suggesting new avenues for functional analysis and improved therapies.

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Conflict of interest statement

Competing financial interests: The authors declare no competing financial interests.

Figures

Figure 1
Figure 1. Regional association plots for novel psoriasis susceptibility loci
This figure depicts LocusZoom-generated association plots for the six psoriasis susceptibility loci identified in the discovery meta-analysis (effective sample size-weighted approach). All but the 15q25.3 locus (f) showed genomewide significant results in the combined meta-analysis.
Figure 2
Figure 2. NFKBIZ mRNA (A) and IκB-zeta protein (B) are induced by IL-17 in an Act1-dependent fashion in human keratinocytes
A. Time courses of TRAF3IP2 (top) and NFKBIZ (bottom) mRNA expression following IL-17 induction. Black bars represent mRNA relative expression levels measured by qPCR in the absence of tetracyline (Tet) while white bars represent levels after silencing TRAF3IP2 expression via Tet-inducible expression of shTRAF3IP2. Bars are mean +/−SEM of 3 independent experiments and ** = p<0.01; Student’s t-test. B, Western blot analysis of time courses of IκB-zeta and Act1 expression (upper panel) and quantitations of IκB-zeta band intensity relative to β-Actin. Bars are mean + SD of 2 independent experiments (lower panel).
See this image and copyright information in PMC

References

    1. Mustonen A, Mattila K, Leino M, Koulu L, Tuominen R. The costs of psoriasis medications. Dermatol Ther (Heidelb) 2013;3:169–77. - PMC - PubMed
    1. Hawro T, et al. Impact of psoriasis severity on family income and quality of life. J Eur Acad Dermatol Venereol. 2014 - PubMed
    1. Nair RP, et al. Genome-wide scan reveals association of psoriasis with IL-23 and NF-kappaB pathways. Nat Genet. 2009;41:199–204. - PMC - PubMed
    1. Sun LD, et al. Association analyses identify six new psoriasis susceptibility loci in the Chinese population. Nat Genet. 2010;42:1005–9. - PMC - PubMed
    1. Ellinghaus E, et al. Genome-wide association study identifies a psoriasis susceptibility locus at TRAF3IP2. Nat Genet. 2010;42:991–5. - PMC - PubMed

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