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Scientific article
Open access
English

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

Published inArthritis & rheumatology, vol. 74, no. 9, p. 1535-1543
Publication date2022-09
First online date2022-05-04
Abstract

Objectives: 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.

Methods: 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 (h2 SNP ) and biologic pathways that differentiate PsA from PsC were identified using Priority Index software. The generalizability of previously published PsA risk prediction pipelines was explored, and a risk prediction model was developed with external validation.

Results: We identified a novel genome-wide significant susceptibility locus for the development of PsA on chromosome 22q11 (rs5754467; P = 1.61 × 10-9 ), and key pathways that differentiate PsA from PsC, including NF-κB signaling (adjusted P = 1.4 × 10-45 ) and Wnt signaling (adjusted P = 9.5 × 10-58 ). The heritability of PsA in this cohort was found to be moderate (h2 SNP = 0.63), which was similar to the heritability of PsC (h2 SNP = 0.61). We observed modest performance of published classification pipelines (maximum area under the curve 0.61), with similar performance of a risk model derived using the current data.

Conclusion: 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.

eng
Keywords
  • Arthritis, Psoriatic / complications
  • Arthritis, Psoriatic / genetics
  • Biological Products
  • Case-Control Studies
  • Genetic Predisposition to Disease / genetics
  • Humans
  • Psoriasis / complications
  • Psoriasis / genetics
  • Risk Factors
Citation (ISO format)
SOOMRO, Mehreen et al. Comparative Genetic Analysis of Psoriatic Arthritis and Psoriasis for the Discovery of Genetic Risk Factors and Risk Prediction Modeling. In: Arthritis & rheumatology, 2022, vol. 74, n° 9, p. 1535–1543. doi: 10.1002/art.42154
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Article (Published version)
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Identifiers
ISSN of the journal2326-5191
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Technical informations

Creation12/06/2022 3:45:53 PM
First validation05/22/2023 5:33:49 PM
Update time05/22/2023 5:33:49 PM
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