Genetic signature to provide robust risk assessment of psoriatic arthritis development in psoriasis patients.
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Abstract | Psoriatic arthritis (PsA) is a complex chronic musculoskeletal condition that occurs in ~30% of psoriasis patients. Currently, no systematic strategy is available that utilizes the differences in genetic architecture between PsA and cutaneous-only psoriasis (PsC) to assess PsA risk before symptoms appear. Here, we introduce a computational pipeline for predicting PsA among psoriasis patients using data from six cohorts with >7000 genotyped PsA and PsC patients. We identify 9 new loci for psoriasis or its subtypes and achieve 0.82 area under the receiver operator curve in distinguishing PsA vs. PsC when using 200 genetic markers. Among the top 5% of our PsA prediction we achieve >90% precision with 100% specificity and 16% recall for predicting PsA among psoriatic patients, using conditional inference forest or shrinkage discriminant analysis. Combining statistical and machine-learning techniques, we show that the underlying genetic differences between psoriasis subtypes can be used for individualized subtype risk assessment. |
Year of Publication | 2018
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Journal | Nat Commun
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Volume | 9
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Issue | 1
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Pages | 4178
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Date Published | 2018 10 09
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ISSN | 2041-1723
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DOI | 10.1038/s41467-018-06672-6
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PubMed ID | 30301895
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PubMed Central ID | PMC6177414
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Grant list | K01 AR072129 / AR / NIAMS NIH HHS / United States
R01 AR042742 / AR / NIAMS NIH HHS / United States
R01 AR063611 / AR / NIAMS NIH HHS / United States
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