{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T12:59:59Z","timestamp":1790341199701,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82204125"],"award-info":[{"award-number":["82204125"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013105","name":"Shanghai Rising-Star Program","doi-asserted-by":"publisher","award":["2024QA2701000"],"award-info":[{"award-number":["2024QA2701000"]}],"id":[{"id":"10.13039\/501100013105","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Proteomics Clinical Apps"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:sec>\n                    <jats:title>ABSTRACT<\/jats:title>\n                    <jats:p>The absence of robust biomarkers for early detection of severe liver disease (SLD) highlights the critical need for high\u2010throughput proteomics\u2010driven discovery. In this prospective cohort study, we aimed to identify plasma protein signatures associated with incident SLD and assess their clinical utility. Using the large\u2010scale Olink Explore 1536 platform, we quantified 1461 plasma proteins in 46951 participants from the UK Biobank community\u2010based cohort without baseline liver disease. Over a median follow\u2010up of 14.1 years, we identified 490 proteins significantly associated with incident SLD risk. Growth differentiation factor 15 (GDF15) emerged as the strongest predictor, achieving a C\u2010index of 0.80 and outperforming conventional clinical indices (LiverRisk score: 0.75; FIB\u20104: 0.68; APRI: 0.68). Temporal trajectories revealed that GDF15 levels began increasing up to 10 years before diagnosis, with progressive elevation as the diagnosis timepoint approached. Mendelian randomization analysis supported genetic associations linking higher protein levels of GDF15, FABP1, SPON2, CHI3L1, and PIGR with SLD risk. Our large\u2010scale proteome\u2010wide study not only reveals significant proteomic changes preceding SLD diagnosis but also establishes GDF15 as both a promising preclinical biomarker, opening new avenues for early intervention in at\u2010risk individuals.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/prca.70055","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T07:22:11Z","timestamp":1789024931000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Large\u2010Scale Plasma Proteomics Reveals Preclinical Biomarkers of Incident Severe Liver Disease"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-0664-9841","authenticated-orcid":false,"given":"Shuzhen","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Epidemiology School of Public Health Key Laboratory of Public Health Safety (Fudan University) Ministry of 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