Genome-wide association analysis identifies three psoriasis susceptibility loci

Nat Genet. 2010 Nov;42(11):1000-4. doi: 10.1038/ng.693. Epub 2010 Oct 17.

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).

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Psoriatic / genetics
  • Case-Control Studies
  • DNA-Binding Proteins / genetics
  • F-Box Proteins / genetics
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study*
  • Genotype
  • Germany
  • Humans
  • I-kappa B Proteins / genetics
  • Michigan
  • NF-KappaB Inhibitor alpha
  • Newfoundland and Labrador
  • Nitric Oxide Synthase Type II / genetics
  • Ontario
  • Polymorphism, Single Nucleotide*
  • Proteasome Endopeptidase Complex / genetics
  • Psoriasis / genetics*

Substances

  • DNA-Binding Proteins
  • F-Box Proteins
  • FBXL19 protein, human
  • I-kappa B Proteins
  • NFKBIA protein, human
  • NF-KappaB Inhibitor alpha
  • NOS2 protein, human
  • Nitric Oxide Synthase Type II
  • PSMA6 protein, human
  • Proteasome Endopeptidase Complex