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Identification of loci associated with late‐onset psoriasis using dense genotyping of immune‐related regions
Author(s) -
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.
Publication year - 2015
Publication title -
british journal of dermatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.304
H-Index - 179
eISSN - 1365-2133
pISSN - 0007-0963
DOI - 10.1111/bjd.13340
Subject(s) - psoriasis , genotyping , age of onset , genome wide association study , genetics , biology , single nucleotide polymorphism , imputation (statistics) , linkage disequilibrium , genetic association , disease , genotype , immunology , medicine , gene , computer science , machine learning , missing data
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 SNP 2 HLA and stepwise logistic regression analysis was performed for markers spanning the human leucocyte antigen gene region. Results Two loci ( HLA ‐ C and IL 12B ) 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 ( TRAF 3 IP 2 , IL 23R , RNF 114 , IFIH 1 , IL 23A 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 IL 1R1 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.