Genetic signature to provide robust risk assessment of psoriatic arthritis development in psoriasis patients

Nat Commun. 2018 Oct 9;9(1):4178. doi: 10.1038/s41467-018-06672-6.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Psoriatic / genetics*
  • Biomarkers / metabolism
  • Cohort Studies
  • Enhancer Elements, Genetic / genetics
  • Gene Expression Profiling*
  • Genetic Loci
  • Humans
  • Meta-Analysis as Topic
  • Risk Assessment*

Substances

  • Biomarkers