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Identification of Loci Associated with Late-Onset Psoriasis Using Dense Genotyping of Immune-Related Regions.

HĂ©bert, H L; Bowes, J; Smith, Rh L L; Flynn, E; Parslew, R; Alsharqi, A; McHugh, N J; Barker, J N W N; Griffiths, C E M; Barton, A; Warren, R B

The British journal of dermatology. 2014;.

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Abstract

BACKGROUND: Chronic plaque psoriasis can be sub-divided into two groups according to 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 Caucasian genome-wide association studies, whilst few studies have investigated genetic susceptibility to late-onset psoriasis. OBJECTIVES: The aim of the current study was to characterise the genetics underpinning late-onset psoriasis. METHODS: We genotyped 543 late-onset psoriasis cases and 4,373 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 HLA gene region. RESULTS: Two loci (HLA-C and IL12B) previously associated with early-onset psoriasis showed significant association at genome-wide threshold in the current study (P<5x10(-8) ). Six more loci (TRAF3IP2, IL23R, ZNF313, IFIH1, IL23A and HLA-A) showed study-wide significant association (P<2.3x10(-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. CONCLUSION: This is the largest study to date of genetic loci in late-onset psoriasis and demonstrates the overlap that exists with early-onset psoriasis, but also suggests that some loci are associated exclusively with late-onset psoriasis. This article is protected by copyright. All rights reserved.

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Digital Object Identifier:
10.1111/bjd.13340
Pubmed Identifier:
25124732
Access state:
Active

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Record metadata

Manchester eScholar ID:
uk-ac-man-scw:237719
Created by:
Sewell, Carol
Created:
23rd October, 2014, 11:00:02
Last modified by:
Sewell, Carol
Last modified:
23rd October, 2014, 11:00:02

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