The Genetics of Psoriasis and Psoriatic Arthritis

Psoriatic arthritis (PsA) is an inflammatory arthritis that manifests in 20-30% of patients diagnosed with psoriasis. Epidemiologic studies suggest a substantial genetic contribution to PsA. There is a strong need for genome-wide association studies (GWAS) on PsA patients, including PsA-weighted or specific variants, and a need for a better understanding of the relevance of HLA alleles in disease expression. Interferon signaling and the NF-kB cascade play roles in PsA, and there are genetic differences between purely cutaneous psoriasis (PsC) and PsA. Psoriasis susceptibility genes for which putative functional coding variants in TYK2 and TRAF3IP2 are strongly associated with PsC and PsA, and neutrophil extracellular traps (NETs) promote Th17 induction in an Act1 D10N-dependent fashion. Genomics and serological factors may also predict treatment response in tumor necrosis factor inhibitors (TNFIs) in PsA, and genetics may play a role in treatment response to TNFIs. Collaborations through GRAPPA are essential to increase study population size, which will enhance the ability to detect the genetic variants that create a predisposition to psoriatic disease and to predict response to biological therapy.