Global transcriptional analysis of psoriatic skin and blood confirms known disease-associated pathways and highlights novel genomic “hot spots” for differentially expressed genes

There are major gaps in our knowledge regarding the exact mechanisms and genetic basis of psoriasis. To investigate the pathogenesis of psoriasis, gene expression in 10 skin (5 lesional, 5 nonlesional) and 11 blood (6 psoriatic, 5 nonpsoriatic) samples were examined using Affymetrix HG-U95A microarrays. We detected 535 (425 upregulated, 110 downregulated) DEGs in lesional skin at 1% false discovery rate (FDR). Combining nine microarray studies comparing lesional and nonlesional psoriatic skin, 34.5% of dysregulated genes were overlapped in multiple studies. We further identified 20 skin and 2 blood associated transcriptional “hot spots” at specified genomic locations. At 5% FDR, 11.8% skin and 10.4% blood DEGs in our study mapped to one of the 12 PSORS loci. DEGs that overlap with PSORS loci may offer prioritized targets for downstream genetic fine mapping studies. Novel DEG “hot spots” may provide new targets for defining susceptibility loci in future studies.

► We examined global gene expression of peripheral blood and skin in psoriatic patients.
► We identified 535 differentially expressed genes (FDR< 1%) using HG-U95A microarrays.
► Comparing nine microarray studies, 34.5% of the DEGs overlapped multiple studies.
► We identified 20 skin and 2 blood transcriptional “hot spots” (p< 0.0001).
► 11.8% skin and 10.4% blood DEGs in our study mapped to one of the 12 PSORS loci.