Faye Orcales

Psoriasis is a chronic immune-mediated skin disease associated with a polygenic basis of inheritance. Using a multi-ethnic cohort, we evaluated polygenic risk scores (PRS) including human leukocyte antigen (HLA) and non-HLA components. We found associations to multiple clinical phenotypes, with many being ethnicity specific.

Psoriasis is a chronic, immune-mediated inflammatory skin disease associated with a polygenic mode of inheritance. In this study, we used a multi-ethnic psoriasis cohort to investigate polygenic risk score (PRS) associations with clinical phenotypes. We collected patient data and Affymetrix genome-wide SNP data from a cohort of 607 psoriasis patients and calculated an 88-loci PRS (PRS-ALL), also partitioned between genetic loci within the HLA region (PRS-HLA; 11 SNPS) and loci outside the HLA region (PRS-NoHLA; 77 SNPS). We used t-test and logistic regression to analyze the association of PRS with various clinical phenotypes. We found that PRS-HLA and PRS-noHLA had differing effects on psoriasis age of onset, psoriatic arthritis, body location, subtype, environmental triggers, cardiovascular comorbidities, and response to phototherapy. In some cases these PRS associations were ethnicity specific. Overall, these results show that the genetic basis for clinical manifestations of psoriasis are driven by distinct HLA and non-HLA effects, and that these PRS associations can be dependent on ethnicity.