Psoriasis: a complex clinical and genetic disorder.

Psoriasis is associated with arthritis in approximately 10% of patients. The skin disease and arthritis have a strong but complex genetic component. Several susceptibility loci have been reported including one major locus that maps very close to the human leukocyte antigen-C gene on chromosome 6p. No causative gene has so far been conclusively identified. A recent genetic analysis that only included patients with psoriatic arthritis revealed a highly significant susceptibility locus on chromosome 16q approximately 20 cM from the NOD2 gene that has been associated with Crohn's disease. This locus was barely detectable when the entire cohort of psoriasis patients was analyzed as a homogeneous entity. A further clinical stratification of psoriasis patients has revealed novel strongly suggestive loci and also increased the logarithm of the odds scores of some previously reported loci. It is concluded that a careful documentation of clinical features and phenotypic stratification may help to analyze complex genetic disorders.