Atopic Polygenic Risk Score Is Associated with Paradoxical Eczema Developing in Patients with Psoriasis Treated with Biologics.
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Khan, Adnan R.
Smith, Catherine H.
Griffiths, Christopher E. M.
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.
Research Subject Categories::MEDICINE::Dermatology and venerology,clinical genetics, internal medicine::Dermatology and venerology , Research Subject Categories::NATURAL SCIENCES::Biology::Cell and molecular biology::Genetics
Al-Janabi A, Eyre S, Foulkes AC, Khan AR, Dand N, Burova E, DeSilva B, Makrygeorgou A, Davies E, Smith CH, Griffiths CEM, Morris AP, Warren RB; BSTOP Study Group and the BADBIR Study Group. Atopic Polygenic Risk Score Is Associated with Paradoxical Eczema Developing in Patients with Psoriasis Treated with Biologics. J Invest Dermatol. 2023 Aug;143(8):1470-1478.e1. doi: 10.1016/j.jid.2023.01.021. Epub 2023 Feb 15. PMID: 36804406.