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. 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. What's already known about this topic? Chronic plaque psoriasis can be dichotomized into early-onset (onset < 40 years) and late-onset (onset ≥ 40 years) subtypes. Genetic studies have so far focused on early-onset psoriasis, identifying 36 loci in white populations. Late-onset psoriasis has generally been neglected in genetic studies. What does this study add? This is the first genome-wide study to date of a late-onset psoriasis cohort. There is a novel association at IL1R1, which is specific for late-onset psoriasis. There is significant association of eight loci previously identified in early-onset psoriasis, demonstrating overlap between early- and late-onset psoriasis.