Identification of loci associated with late-onset psoriasis using dense genotyping of immune-related regions

Br J Dermatol. 2015 Apr;172(4):933-9. doi: 10.1111/bjd.13340. Epub 2015 Feb 5.


Background: Chronic plaque psoriasis can be subdivided into two groups according to the age of onset: type 1 (early onset, before 40 years) and type 2 (late onset, at or beyond 40 years). So far, 36 genetic loci have been associated with early-onset psoriasis in genome-wide association studies of white populations, while few studies have investigated genetic susceptibility to late-onset psoriasis.

Objectives: To characterize the genetics underpinning late-onset psoriasis.

Methods: We genotyped 543 cases of late-onset psoriasis and 4373 healthy controls using the Immunochip array, a dense genotyping chip containing single-nucleotide polymorphisms previously associated with autoimmune diseases. Imputation using SNP2HLA and stepwise logistic regression analysis was performed for markers spanning the human leucocyte antigen gene region.

Results: Two loci (HLA-C and IL12B) previously associated with early-onset psoriasis showed significant association at a genome-wide threshold in the current study (P < 5 × 10(-8)). Six more loci (TRAF3IP2, IL23R, RNF114, IFIH1, IL23A and HLA-A) showed study-wide significant association (P < 2·3 × 10(-5); calculated using Genetic type 1 error calculator). Additionally, we identified an association at IL1R1 on chromosome 2q13, which is not associated with early-onset disease.

Conclusions: This is the largest study to date of genetic loci in late-onset psoriasis, and demonstrates the overlap that exists with early-onset psoriasis. It also suggests that some loci are associated exclusively with late-onset psoriasis.

Publication types

  • Clinical Study
  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Female
  • Genetic Loci / genetics*
  • Genetic Loci / immunology
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • Humans
  • Late Onset Disorders / genetics
  • Late Onset Disorders / immunology
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide / genetics
  • Psoriasis / genetics*
  • Psoriasis / immunology