Atopic polygenic risk score is associated with paradoxical eczema developing in psoriasis patients treated with biologics.

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2023
Authors
DeSilva, Bernadette
Al-Janabi, Ali
Foulkes, Amy C
Khan, Adnan R
Dand, Nick
Burova, Ekaterina
Makrygeorgou, Areti
Davies, Emily
Smith, Catherine
Griffiths, Christopher Em
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Research Projects
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Biologic therapies for psoriasis can cause paradoxical eczema. The role of genetic factors in its pathogenesis are unknown. To identify risk variants, we conducted a genome-wide association study (GWAS) of 3212 psoriasis patients, of whom 88 developed paradoxical eczema. Two lead single nucleotide polymorphisms (SNPs) reached genome-wide significance (P = -8) for association with paradoxical 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 (PRS) for atopic eczema, (PRSAE), general atopic disease (PRSAT) or a combination (PRSCO) which were tested for association with paradoxical eczema. Improvement over a clinical risk model was assessed by the area under the curve (AUC). All three atopy PRS were associated with paradoxical eczema (P ) which were tested for association with paradoxical eczema. Improvement over a clinical risk model was assessed by the area under the curve (AUC). All three atopy PRS were associated with paradoxical eczema (P CO had the strongest association (OR 1.83, 95% CI 1.17-2.84, P = 0.0078). Including atopic PRS in the multivariable model including age, sex, atopic background and psoriatic arthritis history, increased the AUC from 0.671 to 0.681-0.686. Atopic genetic burden is associated with paradoxical eczema occurring in biologic-treated psoriasis patients, indicating shared underlying mechanisms. Incorporating genetic risk may improve treatment outcome prediction models for psoriasis.
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Journal of Investigative Dermatology