IDENTIFICATION OF A MAJOR SUSCEPTIBILITY LOCUS ON CHROMOSOME 6P AND EVIDENCE FOR FURTHER DISEASE LOCI REVEALED BY A 2-STAGE GENOME-WIDE SEARCH IN PSORIASIS

Psoriasis is a common chronic inflammatory disorder of the skin, To fu rther understand the pathogenesis of psoriasis we have chosen to inves tigate the molecular genetic basis of the disorder, We have used a two -stage approach to search the human genome for the location of genes c onferring susceptibility to psoriasis, using a total of 106 affected s ibling pairs identified from 68 independent families, As over a third of the extended kindreds included affected relatives besides siblings, in addition to an analysis of allele sharing between affected sibling pairs, a novel linkage strategy was applied that extracts full non-pa rametric information, Four principal regions of possible linkage were identified on chromosomes 2, 8, 20 (p <0.005) and markers from the MHC region at 6p21 (p <0.0000006) for which significant evidence of linka ge disequilibrium was also observed (p <0.00002), Whilst data from lim ited case control associations exist to implicate the MHC, the results of this genome wide analysis demonstrate that, at least in the popula tion studied, a gene or genes located within the MHC and close to the class 1 HLA loci, represent the major determinant of the genetic basis of psoriasis.