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Integration of proteomic and genomic data provides an unprecedented opportunity to identify predictive biomarkers and therapeutic targets for PsD. Here, through systemic genetic analyses, expression validation, and prospective cohort study, CDSN and PRSS8 were identified as candidate biomarkers and potential therapeutic targets for PsD. Individuals with higher levels of CDSN and PRSS8 were nearly three times more likely to develop PsD compared to the general population. It develops prediction models in adults without PsD at baseline from the UK Biobank. Combining CDSN and PRSS8 with demographics produced desirable predictions for PsD (area under the curve (AUC) = 0.80) and exhibited high specificity.\u00a0Moreover, PRSS8 and CDSN were both predominantly localized in keratinocytes, and in vivo gene silencing of these proteins significantly reduced PsD\u2010like skin lesions and systemic inflammatory markers. The findings strongly suggested that CDSN and PRSS8 are promising biomarkers for PsD onset and progression, providing a 12\u2010year risk assessment window and potential as novel therapeutic targets. These results had important implications for screening high\u2010risk populations and facilitating early intervention for PsD.<\/jats:p>","DOI":"10.1002\/advs.202514130","type":"journal-article","created":{"date-parts":[[2025,12,3]],"date-time":"2025-12-03T04:01:11Z","timestamp":1764734471000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Population\u2010Based Multi\u2010Omics and Cohort Study Identifying Predictive Biomarkers and Therapeutic Targets for Psoriatic Disease"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-6542-4704","authenticated-orcid":false,"given":"Tianxing","family":"Wu","sequence":"first","affiliation":[{"name":"Clinical Research Centre Zhujiang Hospital Southern Medical University  Guangzhou Guangdong 510260 China"},{"name":"Institute of Molecular Immunology Guangdong Provincial Key Laboratory of Immune Regulation and Immunotherapy School of Laboratory 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