Background and design: Psoriasis is a member of a class of common, HLA-associated conditions in which disease susceptibility appears to be heritable. However, the mode of inheritance of these diseases has been difficult to define in simple mendelian terms. Psoriasis displays one of the strongest HLA associations of this class of diseases. However, only a small fraction of those who carry the implicated HLA susceptibility alleles develop disease, and it has proven difficult to demonstrate that the HLA associations observed are due to formal genetic linkage between the disease and the HLA locus. Although the role of environmental factors in psoriasis and these other diseases cannot be denied, the participation of additional genes, not necessarily linked to HLA, has long been suspected.
Observations: Epidemiologic and immunogenetic data are reviewed and analyzed, which demonstrate that a predisposition to psoriasis is heritable, and which implicate genes of the HLA locus as necessary but not sufficient determinants of psoriasis. Recent developments in human genome research are described, which make possible a systematic search for additional genetic determinants of psoriasis, including those unlinked to HLA.
Conclusions: As one of the most common, most heritable, and most highly HLA-associated examples of this class of HLA-associated diseases, psoriasis represents an ideal target for the application of this emerging genomic technology.