A catalog of potential putative functional variants in psoriasis genome-wide association regions.

Abstract

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.