Psoriasis is an immune-mediated inflammatory disease with a genetic component, characterized by dysregulation of cytokine signaling and activation of T lymphocytes. This study investigated genetic variants associated with psoriasis, psoriatic arthritis (PsA), and response to tumor necrosis factor alpha (TNF-α) inhibitors (adalimumab, infliximab, and etanercept) in a Russian cohort. A genome-wide association study (GWAS) was conducted in 1026 psoriasis patients and 9212 controls using Infinium Global Screening Array-24 v3.0 microarrays. Exploratory analyses of treatment response (n = 48) and PsA (n = 96) were performed without covariate adjustment or explicit modeling of population structure. Polygenic risk scores (PRS) were derived from internally estimated effect sizes in a split-sample design. The GWAS replicated a robust association in the major histocompatibility complex (MHC) region (rs12189871 near HLA-C, p = 3.2 × 10−50, OR = 2.99 2.59–3.45). Additional loci included variants in ZC3H8 and PLCL2. Nominal signals were observed for IL18R1/IL18RAP in treatment response (including rs17027071) and for RCL1 and FBLIM1 in PsA; these findings remain exploratory. PRS demonstrated moderate predictive performance (AUC = 0.6355) and should be interpreted with caution given the study design. Overall, the results highlight a strong MHC signal in psoriasis, while findings for PsA and treatment response remain hypothesis-generating and require independent validation.
Karamova et al. (Fri,) studied this question.