Atopic polygenic risk score is associated with paradoxical eczema developing in psoriasis patients treated with biologics.
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Authors
Al-Janabi, A.
Eyre, S.
Foulkes, A. C.
Khan, A. R.
Dand, N.
Burova, E.
DeSilva, B.
Makrygeorgou, A.
Davies, E
Smith, C. H.
Issue Date
2023
Type
Scientific Paper
Language
Keywords
Research Subject Categories::MEDICINE::Dermatology and venerology,clinical genetics, internal medicine::Dermatology and venerology
Alternative Title
Abstract
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 × 10−8) for association with paradoxical eczema: rs192705221 (near UNC5B, P = 9.52 × 10−10) and rs72925168 (within SLC1A2, P = 1.66 × 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.
Description
Citation
Al-Janabi A, Eyre S, Foulkes A ... Atopic Polygenic Risk Score Is Associated with Paradoxical Eczema Developing in Patients with Psoriasis Treated with Biologics Journal of Investigative Dermatology, 2023; 143, 1470-1478.e1