Comparative Genetic Analysis of Psoriatic Arthritis and Psoriasis for the Discovery of Genetic Risk Factors and Risk Prediction Modeling.

Psoriatic arthritis (PsA) has a strong genetic component, and the identification of genetic risk factors could help identify the ~30% of psoriasis patients at high risk of developing PsA. Our objectives were to identify genetic risk factors and pathways that differentiate PsA from cutaneous-only psoriasis (PsC) and to evaluate the performance of PsA risk prediction models. Genome-wide meta-analyses were conducted separately for 5,065 patients with PsA and 21,286 healthy controls and separately for 4,340 patients with PsA and 6,431 patients with PsC. The heritability of PsA was calculated as a single-nucleotide polymorphism (SNP)-based heritability estimate (h We identified a novel genome-wide significant susceptibility locus for the development of PsA on chromosome 22q11 (rs5754467; P = 1.61 × 10 Key biologic pathways associated with the development of PsA were identified, but the investigation of risk classification revealed modest utility in the available data sets, possibly because many of the PsC patients included in the present study were receiving treatments that are also effective in PsA. Future predictive models of PsA should be tested in PsC patients recruited from primary care.

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© 2022 The Authors. Arthritis & Rheumatology published by Wiley Periodicals LLC on behalf of American College of Rheumatology.