title: Identification of loci associated with late-onset psoriasis using dense genotyping of immune-related regions.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors.affiliation: The Dermatology Centre, Salford Royal NHS Foundation Trust, University of Manchester, Manchester Academic Health Science Centre, Manchester, M6 8HD, U.K; Arthritis Research U.K. Centre for Genetics and Genomics, University of Manchester, Manchester Academic Health Science Centre, Manchester, M13 9PT, U.K.
authors.forename: H L
authors.initials: HL
authors.lastname: Hébert
authors.forename: J
authors.initials: J
authors.lastname: Bowes
authors.forename: Rh Ll
authors.initials: RL
authors.lastname: Smith
authors.forename: E
authors.initials: E
authors.lastname: Flynn
authors.forename: R
authors.initials: R
authors.lastname: Parslew
authors.forename: A
authors.initials: A
authors.lastname: Alsharqi
authors.forename: N J
authors.initials: NJ
authors.lastname: McHugh
authors.forename: J N W N
authors.initials: JN
authors.lastname: Barker
authors.forename: C E M
authors.initials: CE
authors.lastname: Griffiths
authors.forename: A
authors.initials: A
authors.lastname: Barton
authors.forename: R B
authors.initials: RB
authors.lastname: Warren
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D056426:Genetic Loci / Q000235:genetics* / Q000276:immunology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D000067562:Late Onset Disorders / Q000235:genetics / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011565:Psoriasis / Q000235:genetics* / Q000276:immunology