{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T00:53:17Z","timestamp":1768524797756,"version":"3.49.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:00:00Z","timestamp":1768435200000},"content-version":"vor","delay-in-days":14,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AG086379"],"award-info":[{"award-number":["R01AG086379"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,1,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Causal mediation analysis investigates whether the effect of an exposure on an outcome operates through intermediate variables known as mediators. Although progress has been made in high-dimensional mediation analysis, current methods do not reliably control the false discovery rate (FDR) in finite samples, especially when mediators are moderately to highly correlated or follow non-Gaussian distributions. These challenges frequently arise in DNA methylation studies. We introduce CoxMDS, a multiple data splitting method that uses Cox proportional hazards models to identify putative causal mediators for survival outcomes. CoxMDS ensures finite-sample FDR control even in the presence of correlated or non-Gaussian mediators. Through simulations, CoxMDS is shown to maintain FDR control and achieve higher statistical power compared with existing approaches. In applications to DNA methylation data with survival outcomes, CoxMDS identified eight CpG sites in The Cancer Genome Atlas that are consistent with the hypothesis that DNA methylation may mediate the effect of smoking on lung cancer survival, and two CpG sites in the Alzheimer\u2019s Disease Neuroimaging Initiative that are consistent with the hypothesis that DNA methylation may mediate the effect of smoking on time to Alzheimer\u2019s disease conversion.<\/jats:p>","DOI":"10.1093\/bib\/bbaf730","type":"journal-article","created":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T09:13:37Z","timestamp":1768468417000},"source":"Crossref","is-referenced-by-count":0,"title":["CoxMDS: multiple data splitting for high-dimensional mediation analysis with survival outcomes in epigenome-wide studies"],"prefix":"10.1093","volume":"27","author":[{"given":"Minhao","family":"Yao","sequence":"first","affiliation":[{"name":"Centre for Quantitative Medicine, Duke-NUS Medical School, National University of Singapore , 8 College Road, Singapore 169857 ,","place":["Singapore"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peixin","family":"Tian","sequence":"additional","affiliation":[{"name":"First Affiliated Hospital of Kunming Medical University, Kunming Medical University , 295 Xichang Road, Kunming, Yunnan Province 650032 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xihao","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of North Carolina at Chapel Hill , 135 Dauer Drive, Chapel Hill, NC 27599 ,","place":["United States"]},{"name":"Department of Genetics, University of North Carolina at Chapel Hill , 120 Mason Farm Road, Chapel Hill, NC 27599 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shijia","family":"Bian","sequence":"additional","affiliation":[{"name":"Department of Biostatistics and Bioinformatics, Emory University , 1518 Clifton Road, Atlanta, GA 30322 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gao","family":"Wang","sequence":"additional","affiliation":[{"name":"Center for Statistical Genetics, Gertrude H. Sergievsky Center, Columbia University Medical Center , 630 West 168th Street, New York, NY 10032 ,","place":["United States"]},{"name":"Department of Neurology, Columbia University , 710 West 168th Street, New York, NY 10032 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yian","family":"Gu","sequence":"additional","affiliation":[{"name":"Center for Statistical Genetics, Gertrude H. Sergievsky Center, Columbia University Medical Center , 630 West 168th Street, New York, NY 10032 ,","place":["United States"]},{"name":"Department of Neurology, Columbia University , 710 West 168th Street, New York, NY 10032 ,","place":["United States"]},{"name":"Taub Institute on Alzheimer\u2019s Disease and the Aging Brain, Columbia University , 630 West 168th Street, New York, NY 10032 ,","place":["United States"]},{"name":"Department of Epidemiology, Columbia University , 722 West 168th Street, New York, NY 10032 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Navas-Acien","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences, Columbia University , 722 West 168th Street, New York, NY 10032 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Badri N","family":"Vardarajan","sequence":"additional","affiliation":[{"name":"Department of Neurology, Columbia University , 710 West 168th Street, New York, NY 10032 ,","place":["United States"]},{"name":"Taub Institute on Alzheimer\u2019s Disease and the Aging Brain, Columbia University , 630 West 168th Street, New York, NY 10032 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel W","family":"Belsky","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, Columbia University , 722 West 168th Street, New York, NY 10032 ,","place":["United States"]},{"name":"Robert N. Butler Columbia Aging Center, Columbia University , 722 West 168th Street, New York, NY 10032 ,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary W","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Environmental Health Sciences , Columbia University, 722 West 168th Street, New York, NY 10032,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea A","family":"Baccarelli","sequence":"additional","affiliation":[{"name":"Office of the Dean, Harvard T.H. 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