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Psoriasis is a common inflammatory skin disease, with considerable genetic contribution. Genome-wide association studies have successfully identified a number of genomic regions for the risk of psoriasis. However, it is challenging to pinpoint the functional causal variants and then further decipher the genetic mechanisms underlying each region. In order to prioritize potential functional causal variants within psoriasis susceptibility regions, we integrated the genetic association findings and functional genomic data publicly available, i.e. histone modifications in relevant immune cells. We characterized a pervasive enrichment pattern of psoriasis variants in five core histone marks across immune cells/tissues. We discovered that genetic alleles within psoriasis association regions might influence gene expression levels through significantly affecting the binding affinities of 17 transcription factors. We established a catalog of 654 potential functional causal variants for psoriasis and suggested that they significantly overlapped with causal variants for autoimmune diseases. We identified potential causal variant rs79824801 overlay with the peaks of five histone marks in primary CD4+ T cells. Its alternative allele affected the binding affinity of transcription factor IKZF1. This study highlights the complex genetic architecture and complicated mechanisms for psoriasis. The findings will inform the functional experiment design for psoriasis. [ABSTRACT FROM AUTHOR]

With numbers of common variants identified mainly through genome-wide association studies (GWASs), there is great interest in incorporating the findings into screening individuals at high risk of psoriasis. The purpose of this study is to establish genetic prediction models and evaluate its discriminatory ability in psoriasis in Han Chinese population. We built the genetic prediction models through weighted polygenic risk score (PRS) using 14 susceptibility variants in 8,819 samples. We found the risk of psoriasis among individuals in the top quartile of PRS was significantly larger than those in the lowest quartile of PRS (OR = 28.20, P < 2.0×10-16). We also observed statistically significant associations between the PRS, family history and early age onset of psoriasis. We also built a predictive model with all 14 known susceptibility variants and alcohol consumption, which achieved an area under the curve statistic of ~ 0.88. Our study suggests that 14 psoriasis known susceptibility loci have the discriminating potential, as is also associated with family history and age of onset. This is the genetic predictive model in psoriasis with the largest accuracy to date. [ABSTRACT FROM AUTHOR]