Abstract
The relationship between proteomics and atopic dermatitis (AD) remains underexplored but holds significant potential for therapeutic intervention. We analyzed data from a longitudinal cohort of 51,458 UK Biobank participants to investigate the relationship between AD risk and serum levels of 2923 proteins. Multivariate Cox regression was initially applied to evaluate associations between protein concentrations and AD incidence. Subsequently, two-sample Mendelian randomization (MR), summary-data-based MR, and colocalization analyses were conducted to establish genetic associations with AD. Our analysis identified 23 proteins significantly associated with AD risk. Two-sample MR further validated ten proteins exhibiting robust causal relationships with AD. Comprehensive assessments using summary-data-based MR, colocalization, and differential expression analyses pinpointed 5 key proteins - CACYBP, CETN3, MOCS2, TNFAIP8, and PVALB - with potential protective effects against AD. A novel protein-based scoring system, integrating these biomarkers with inflammatory markers, achieved superior predictive accuracy for AD onset (area under the curve = 0.833), outperforming both the polygenic risk score and eosinophil percentage. This extensive proteomic and genetic study within a European adult cohort provides compelling causal evidence for several proteins as potential biomarkers for AD, offering new avenues for early diagnosis and therapeutic development.