A genome-wide search for genes predisposing to familial psoriasis by usinga stratification approach

We have performed a genome scan, using markers spaced by 10 cM, in the sear ch for psoriasis-susceptibility loci. The family material of 134 affected s ibling pairs was ascertained on the basis of a population genetic study in which 65% of the probands had two healthy parents. Genotyping results were analyzed for non-random excessive allele-sharing between sib pairs by using GENEHUNTER ver 1.1. A stratification approach was applied to increase the homogeneity of the material by means of an operational definition of joint complaints among affected individuals. Significant linkage to the human leu kocyte antigen region on chromosome 6p in a cohort including 42 families wi thout joint complaints (nonparametric linkage score of 2.83, P=0.002) stron gly supported the validity of this operational definition as it replicated results from an earlier linkage report with similar stratification criteria . New candidate regions on chromosomes 3 and 15 were identified. The highes t non-parametric linkage values in this study, 2.96 (P=0.0017) and 2.89 (P= 0.0020), were reached on chromosome 15 in a subgroup with joint complaints and on chromosome 3 in a subgroup without joint complaints. In addition, co nfirmation of previously reported loci was established on chromosomes 4q, 6 p, and 17q. This study indicates that distinct disease loci might be involv ed in psoriasis etiology for various phenotypes.