Genomewide scan in german families reveals evidence for a novel psoriasis-susceptibility locus on chromosome 19p13

Abstract

Psoriasis is a common chronic inflammatory skin disease with a strong genetic component. Few psoriasis-susceptibility loci have been reported, and only two have been confirmed in independent data sets. This article reports results of a genomewide scan that was performed, using 370 microsatellite markers, for psoriasis-susceptibility loci in 32 German extended families, comprising 162 affected and 195 unaffected individuals. Nonparametric linkage analysis of all families provided strong evidence for a novel psoriasis-susceptibility locus on chromosome 19p (Zlr=3.50; P=.0002). Parametric analysis revealed a heterogeneity LOD score of 4.06, corresponding to a genomewide significance level of.037, under the assumption of a recessive model with high disease-allele frequency and 66% as the proportion of linked families. This study confirms linkage of psoriasis to the HLA region on chromosome 6p and suggests additional regions on chromosomes 8q and 21q for further investigations.

Figure 1

Summary of the genome scan for psoriasis-susceptibility loci in 32 German extended families. The figure shows nonparametric multipoint GENEHUNTER PLUS Z_lr (A) and LOD* score (B), across all autosomes, from pter to qter. Dotted lines indicate chromosome boundaries.

Figure 2

Linkage analysis on chromosome 19, showing GENEHUNTER nonparametric LOD* score (Z_all) and HLOD score, assuming a recessive model with high disease-allele frequency, as well as GENEHUNTER PLUS Z_lr and nonparametric LOD score. Markers are arranged in map order, according to the final Généthon human linkage map (Dib et al. 1996).