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Genetics Analysis of Psoriasis: The GAP study

Richard Trembath

CEM Griffiths, Andre Reis, Juha Kere.

Psoriasis is a common and disfiguring skin complaint affecting more than a million adults in the UK alone. The disorder is considered likely to arise due to the combination of an inherited predisposition (many affected subjects have similarly affected close relatives) together with poorly understood environmental trigger factors. Psoriasis Vulgaris is the most common (>90%) form of psoriasis which is a chronic, inflammatory skin disorder characterised by the presence of inflamed scaly cutaneous plaques sharply demarcated from the surrounding normal. Inflammation may readily be triggered by trauma and/or pressure (Koebner phenomena) skin patches that can cover a substantial part of the body.

Psoriasis Vulgaris (PV) is strongly clustered in families with a sibling risk of 8-10% against a population prevalence of 1-2 %. The risk to first, second and third degree relatives declines rapidly and as such has been interpreted as indicative of an epistatic, multiplicative complex mode of inheritance. Genome-wide linkage scans have mapped at least 9 non-MHC disease regions (PSORS2-10), but efforts to validate these findings have often generated conflicting results.

We propose to perform an initial scan on 3000 unrelated subjects ascertained from around the UK. We will seek confirmation and replication of the initial associations through the analysis of European samples (n= 3000) each with locally derived control cohorts. The consortium has additional resources which add value to the GAP study. These include serum samples on many of the patients and ethical permission to collect skin biopsies (see appendix). These will aid considerably in studies to validate identified genetic associations.