THE GENETICS OF PSORIASIS

Background and Design: Psoriasis is a member of a class of common, HLA -associated conditions in which disease susceptibility appears to be h eritable. 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 susceptibi lity alleles develop disease, and it has proven difficult to demonstra te that the HLA associations observed are due to formal genetic linkag e between the disease and the HLA locus. Although the role of environm ental 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 predispositi on to psoriasis is heritable, and which implicate genes of the HLA loc us as necessary but not sufficient determinants of psoriasis. Recent d evelopments in human genome research are described, which make possibl e a systematic search for additional genetic determinants of psoriasis , including those unlinked to HLA. Conclusions: As one of the most com mon, most heritable, and most highly HLA-associated examples of this c lass of HLA-associated diseases, psoriasis represents an ideal target for the application of this emerging genomic technology.