Original Article
Subject Categories: Genetics
Journal of Investigative Dermatology (2005) 124, 1177–1185; doi:10.1111/j.0022-202X.2005.23703.x
Genetics of Psoriasis in Iceland: Evidence for Linkage of Subphenotypes to Distinct Loci
Ari Karason*, Johann E Gudjonsson†, Hjörtur H Jónsson*, Valdimar B Hauksson*, E Hjaltey Runarsdottir*, Kari Stefansson*, Helgi Valdimarsson† and Jeffrey R Gulcher*
- *deCODE Genetics, Reykjavik, Iceland
- †Department of Immunology, University National Hospital, Hringbraut, Reykjavik, Iceland
Correspondence: Ari Karason, deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland. Email: ari@decode.is
Received 22 January 2004; Revised 17 August 2004; Accepted 18 August 2004; Published online 3 June 2005.
Abstract
Psoriasis is a chronic inflammatory skin disease with overlapping subphenotypes. It has a strong complex genetic component, but has been problematic to identifying significant loci. We evaluated 1000 patients with chronic plaque psoriasis and documented several subphenotypes. Here we report results of genome-wide linkage scans for psoriasis genes in 238 Icelandic families with 874 patients. MHC linkage was confirmed with LOD score of 10.9. When the entire cohort was analyzed, two other loci with LOD scores of 2.5 and 1.5 were observed on 16q and 4q, respectively. Stratification into subphenotypes revealed additional loci with LOD scores exceeding or approaching significance. A LOD score of 5.7 appeared on 16q in PsA patients with analysis conditioned on parental inheritance. A LOD score of 3.6 on 4q was detected when disease occurred at or older than 17 y, our median cohort age. This locus was defined by a marker near one reportedly displaying significant linkage in a Chinese psoriasis population and near suggestive linkage in a Caucasian population. A LOD of 3.0 was observed on 10q when disease onset occurred in the scalp. Furthermore, clinical stratification either revealed or increased LOD scores when compared to unstratified analysis and some coincided with previous reports.
Keywords:
psoraisis, subphenotypes, linkage, stratification
Abbreviations:
MHC, major histocompatibility molecules; LOD, logarithm of odds ratio; HLA, human leukocyte antigen; POPP, pediatric onset psoriatic patients; AOPP, adult onset psoriatic patients
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