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

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Authors
Al-Janabi, Ali
Eyre, Steve
Foulkes, Amy
Khan, Adnan R.
Dand, Nick
Burova, Ekaterina
Makrygeorgou, Areti
Davies, Emily
Smith, Catherine H.
Griffiths, Christopher E. M.
Issue Date
2023
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Scientific Paper
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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
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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.
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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.
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