Skip to main page content
Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2010 Nov;42(11):1000-4.
doi: 10.1038/ng.693. Epub 2010 Oct 17.

Genome-wide Association Analysis Identifies Three Psoriasis Susceptibility Loci

Affiliations
Free PMC article

Genome-wide Association Analysis Identifies Three Psoriasis Susceptibility Loci

Philip E Stuart et al. Nat Genet. .
Free PMC article

Abstract

We carried out a meta-analysis of two recent psoriasis genome-wide association studies with a combined discovery sample of 1,831 affected individuals (cases) and 2,546 controls. One hundred and two loci selected based on P value rankings were followed up in a three-stage replication study including 4,064 cases and 4,685 controls from Michigan, Toronto, Newfoundland and Germany. In the combined meta-analysis, we identified three new susceptibility loci, including one at NOS2 (rs4795067, combined P = 4 × 10⁻¹¹), one at FBXL19 (rs10782001, combined P = 9 × 10⁻¹⁰) and one near PSMA6-NFKBIA (rs12586317, combined P = 2 × 10⁻⁸). All three loci were also associated with psoriatic arthritis (rs4795067, combined P = 1 × 10⁻⁵; rs10782001, combined P = 4 × 10⁻⁸; and rs12586317, combined P = 6 × 1⁻⁵) and purely cutaneous psoriasis (rs4795067, combined P = 1 × 10⁻⁸; rs10782001, combined P = 2 × 10⁻⁶; and rs12586317, combined P = 1 × 10⁻⁶). We also replicated a recently identified association signal near RNF114 (rs495337, combined P = 2 × 10⁻⁷).

Figures

Figure 1
Figure 1
Evidence for psoriasis association in four genomic regions, including the three novel loci attaining genome-wide significance and the confirmed RNF114 region. The upper portion of each plot depicts association p-values for a meta-analysis of the CASP and Kiel discovery GWAS using 1000G-based imputation, while the lower portion depicts RefSeq genes and LD plots from the phase 2 HapMap-CEU sample. For each region, the most strongly associated replicated SNP is highlighted in red, as are its p-values for the discovery, replication, and combined samples.
Figure 2
Figure 2
Expression data for notable candidate genes within the three psoriasis-associated regions. Log2-transformed levels of mRNA assayed by qRT-PCR are shown for normal (NN), uninvolved (PN), and lesional psoriatic (PP) skin. Figures include both individual measurements (jittered scatterplots) and box-plots summarizing the distribution. Bars and significance levels are shown for all pairwise comparisons of mean mRNA levels that are significant at a nominal (p ≤ 0.05) level.

Similar articles

See all similar articles

Cited by 124 articles

See all "Cited by" articles

References

    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. Ellinghaus E, et al. Genome-wide association study reveals association of psoriasis with TRAF3IP2. Nature Genetics. 2010 in press.
    1. Capon F, et al. Identification of ZNF313/RNF114 as a novel psoriasis susceptibility gene. Hum Mol Genet. 2008;17:1938–45. - PMC - PubMed
    1. Nestle FO, Di Meglio P, Qin JZ, Nickoloff BJ. Skin immune sentinels in health and disease. Nat Rev Immunol. 2009;9:679–91. - PMC - PubMed
    1. Gladman DD. Psoriatic arthritis. In: Koo J, Lee CS, Lebwohl M, Weinstein GD, Gottlieb AB, editors. Moderate to Severe Psoriasis. Informa Health Care; New York: 2009. pp. 239–258.

Publication types

Feedback