{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T23:01:48Z","timestamp":1784934108097,"version":"3.55.0"},"reference-count":50,"publisher":"Oxford University Press (OUP)","issue":"21","license":[{"start":{"date-parts":[[2021,8,3]],"date-time":"2021-08-03T00:00:00Z","timestamp":1627948800000},"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":"NIH","doi-asserted-by":"publisher","award":["UL1 TR002345"],"award-info":[{"award-number":["UL1 TR002345"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R21 AG063370"],"award-info":[{"award-number":["R21 AG063370"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,11,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Motivation<\/jats:title><jats:p>Mediation analysis has become a prevalent method to identify causal pathway(s) between an independent variable and a dependent variable through intermediate variable(s). However, little work has been done when the intermediate variables (mediators) are high-dimensional and the outcome is a survival endpoint. In this paper, we introduce a novel method to identify potential mediators in a causal framework of high-dimensional Cox regression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We first reduce the data dimension through a mediation-based sure independence screening method. A de-biased Lasso inference procedure is used for Cox\u2019s regression parameters. We adopt a multiple-testing procedure to accurately control the false discovery rate when testing high-dimensional mediation hypotheses. Simulation studies are conducted to demonstrate the performance of our method. We apply this approach to explore the mediation mechanisms of 379\u2009330 DNA methylation markers between smoking and overall survival among lung cancer patients in The Cancer Genome Atlas lung cancer cohort. Two methylation sites (cg08108679 and cg26478297) are identified as potential mediating epigenetic markers.<\/jats:p><\/jats:sec><jats:sec><jats:title>Availability and implementation<\/jats:title><jats:p>Our proposed method is available with the R package HIMA at https:\/\/cran.r-project.org\/web\/packages\/HIMA\/.<\/jats:p><\/jats:sec><jats:sec><jats:title>Supplementary information<\/jats:title><jats:p>Supplementary data are available at Bioinformatics online.<\/jats:p><\/jats:sec>","DOI":"10.1093\/bioinformatics\/btab564","type":"journal-article","created":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T19:25:54Z","timestamp":1627586754000},"page":"3815-3821","source":"Crossref","is-referenced-by-count":43,"title":["Mediation analysis for survival data with high-dimensional mediators"],"prefix":"10.1093","volume":"37","author":[{"given":"Haixiang","family":"Zhang","sequence":"first","affiliation":[{"name":"Center for Applied Mathematics, Tianjin University , Tianjin 300072, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yinan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, Northwestern University , Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lifang","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, Northwestern University , Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6562-870X","authenticated-orcid":false,"given":"Cheng","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, University of Nebraska Medical Center , Omaha, NE 68198, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1844-338X","authenticated-orcid":false,"given":"Lei","family":"Liu","sequence":"additional","affiliation":[{"name":"Division of Biostatistics, Washington University in St. Louis , St. Louis, MO 63110, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,8,3]]},"reference":[{"key":"2023051608243995600_btab564-B1","doi-asserted-by":"crossref","first-page":"1173","DOI":"10.1037\/0022-3514.51.6.1173","article-title":"The moderator\u2013mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations","volume":"51","author":"Baron","year":"1986","journal-title":"J. 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