Genetic signature to provide robust risk assessment of psoriatic arthritis development in psoriasis patients
Patrick, M. T., Stuart, P. E., Raja, K., Gudjonsson, J. E., Tejasvi, T., Yang, J., … Tsoi, L. C. (2018). Genetic signature to provide robust risk assessment of psoriatic arthritis development in psoriasis patients. Nature communications, 9(1), 4178. doi:10.1038/s41467-018-06672-6
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.
Medical Subject Headings
Arthritis, Psoriatic; Biomarkers; Cohort Studies; Enhancer Elements, Genetic; Gene Expression Profiling; Genetic Loci; Humans; Meta-Analysis as Topic; Risk Assessment