Figure 5.

We identified 356 genes for which expression was significantly elevated in the lesional skin of patients in proportion to IL12B risk allele carriage (0–4 risk alleles, including rs6887695 G allele and rs3212227 A allele; n = 53 patients; P < 0.05). The heat map shows 30 genes with increased expression in lesional skin from individuals with more IL12B risk alleles (rs6887695 and rs3212227, P < 0.035) and the expression responses of these genes to IFN-γ, IL-17, TNF-α and IL-22 in cultured keratinocytes (A). Expression levels of three representative genes demonstrate a dose-dependent increase in the expression levels in psoriatic skin based on risk allele carriage. The red line denotes the least squares regression estimate with a positive slope in each case. (B) Furthermore, all genes were ranked according to their level of positive association with IL12B risk carriage (rs6887695 and rs3212227), and this list was compared for overlap with gene lists ranked by their level of induction by IFN-γ, IL-17, TNF-α or IL-22 in keratinocytes (C). In each box, the red line shows the level of overlap among the top n genes taken from each list, whereas the gray region outlines the central 95% of the null distribution under a random sampling model (hypergeometric distribution). Larger than expected overlap (for given n) is present, if the red line lies above the gray region, whereas lower than expected overlap (for given n) is present, if the red line lies below the gray region. P-values are based upon the overlap between the top 1000 genes from each gene list.