Details

Autor(en) / Beteiligte

• Hébert, H.L.
• Bowes, J.
• Smith, Rh.Ll
• Flynn, E.
• Parslew, R.
• Alsharqi, A.
• McHugh, N.J.
• Barker, J.N.W.N.
• Griffiths, C.E.M.
• Barton, A.
• Warren, R.B.

Titel

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

Ist Teil von

• British journal of dermatology (1951), 2015-04, Vol.172 (4), p.933-939

Ort / Verlag

England: Blackwell Publishing Ltd

Erscheinungsjahr

2015

Link zum Volltext

Quelle

Wiley Online Library Journals Frontfile Complete

Beschreibungen/Notizen

• Summary 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.