Atopic Polygenic Risk Score Is Associated with Paradoxical Eczema Developing in Patients with Psoriasis Treated with Biologics

Biologic therapies for psoriasis can cause paradoxical eczema. The role of genetic factors in its pathogenesis is unknown. To identify risk variants, we conducted a GWAS of 3,212 patients with psoriasis, of whom 88 developed paradoxical eczema. Two lead SNPs reached genome-wide significance (P < 5 x 10-8) for association with para-doxical eczema: rs192705221 (near UNC5B, P = 9.52 x 10-10) and rs72925168 (within SLC1A2, P = 1.66 x 10-9). Genome-wide significant SNPs from published GWAS were used to generate polygenic risk scores (PRSs) for atopic eczema, general atopic disease, or a combination, which were tested for association with paradoxical eczema. Improvement over a clinical risk model was assessed by the area under the curve. All three atopy polygenic risk scores were associated with paradoxical eczema (P < 0.05); polygenic risk score for a combination of atopic eczema and general atopic disease had the strongest association (OR = 1.83, 95% CI = 1.17-2.84, P= 0.0078). Including atopic polygenic risk scores in the multivariable model, which included age, sex, atopic background, and psoriatic arthritis history, increased the area under the curve from 0.671 to 0.681-0.686. Atopic genetic burden is associated with paradoxical eczema occurring in biologic-treated patients with psoriasis, indicating shared underlying mechanisms. Incorporating genetic risk may improve treatment outcome prediction models for psoriasis.Journal of Investigative Dermatology (2023) 143, 1470e1478; doi:10.1016/j.jid.2023.01.021

Automated summary

Genetic factors play a role in the development of paradoxical eczema in patients with psoriasis receiving biologic therapy. Two lead SNPs (rs192705221 and rs72925168) were found to be associated with paradoxical eczema. Additionally, polygenic risk scores for atopic eczema and general atopic disease were also associated with paradoxical eczema. These findings indicate that atopic genetic burden contributes to the occurrence of paradoxical eczema in psoriasis patients receiving biologic therapy, suggesting shared underlying mechanisms. Incorporating genetic risk may improve treatment outcome prediction models for psoriasis.