Plasma proteomics-based risk scores for psoriasis prediction: a novel approach to early diagnosis

TL;DR

This study introduces a new plasma proteomics-based risk score to improve early diagnosis and prediction of psoriasis by combining proteomic, genetic, and clinical data.

Contribution

The novel contribution is the development of ProtRS-26, a plasma proteomics-based risk score that outperforms existing genetic and clinical models for psoriasis prediction.

Findings

ProtRS-26, built from 26 plasma proteins, significantly improves psoriasis prediction compared to polygenic risk scores and clinical factors alone.

Combining ProtRS-26 with genetic and clinical data further enhances prediction accuracy.

Key proteins in ProtRS-26 are linked to pro-inflammatory pathways and skin biology, with hypertension and obesity identified as major modifiable risk factors.

Abstract

Psoriasis is a chronic immune-mediated inflammatory skin disease with a significant global burden. Current risk assessment lacks integration of proteomic data with genetic and clinical factors. This study aimed to develop a plasma proteomics-based risk score (ProtRS) to improve psoriasis prediction.

Using data from 53,065 UK Biobank (UKB) participants (1,122 psoriasis cases; 51,943 controls), we integrated 2,923 plasma proteins, polygenic risk score (PRS), and seven clinical risk factors. The Least Absolute Shrinkage and Selection Operator (LASSO) algorithm with 10-fold cross-validation identified stable proteins for ProtRS construction. Population Attributable Fractions (PAFs) for risk factors were calculated.

LASSO regression identified 26 highly stable proteins forming ProtRS-26. ProtRS-26 significantly outperformed PRS and clinical risk factors alone. Combining ProtRS-26 with PRS and clinical factors further improved prediction. Key proteins were enriched in pro-inflammatory pathways and skin-derived. PAF analysis identified hypertension and obesity as major modifiable risk factors.

Plasma proteomics significantly enhances psoriasis risk prediction compared to genetic and clinical factors alone. ProtRS-26 provides a robust tool for early screening and personalized prevention.

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