{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T11:43:36Z","timestamp":1753875816935,"version":"3.41.2"},"reference-count":28,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T00:00:00Z","timestamp":1743552000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000002","name":"US National Institutes of Health","doi-asserted-by":"publisher","award":["RF1AG081413","R01AG068191","R01EB034720","R01HL122212","U24AG072122","P30AG066508","P30AG021342"],"award-info":[{"award-number":["RF1AG081413","R01AG068191","R01EB034720","R01HL122212","U24AG072122","P30AG066508","P30AG021342"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,4,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Understanding how biomarkers change in relation to disease pathogenesis is a key area in biomedical research. We propose a semiparametric joint model to analyze the temporal evolution of biomarkers prior to the onset of disease. The model allows for a flexible biomarker trajectory that depends on two time scales: a natural time scale such as age and time to disease onset. In practice, the natural time scale often differs from time-on-study, leading to analytical challenges such as left-truncation bias. We introduce a profile kernel estimating equation\u00a0approach to estimate regression coefficients and unspecified baseline mean trajectory functions. We establish the large-sample properties of the proposed estimators and conduct simulation studies to evaluate their finite-sample performance. Our method is applied to investigate brain biomarker trajectories before the onset of preclinical Alzheimer\u2019s disease. We observed a decline in cortical thickness prior to disease onset across brain regions, with APOE4 carriers showing lower levels compared to non-carriers.<\/jats:p>","DOI":"10.1093\/biomtc\/ujaf064","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T09:00:26Z","timestamp":1748422826000},"source":"Crossref","is-referenced-by-count":0,"title":["Semiparametric joint modeling for biomarker trajectory before disease onset"],"prefix":"10.1093","volume":"81","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6961-5500","authenticated-orcid":false,"given":"Yifei","family":"Sun","sequence":"first","affiliation":[{"name":"Columbia University Department of Biostatistics, , New York, NY 10032 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiwen","family":"Zhao","sequence":"additional","affiliation":[{"name":"Yale University Department of Biostatistics, , New Haven, CT 06520 ,","place":["United 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