{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T20:38:53Z","timestamp":1776285533365,"version":"3.50.1"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"20","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2016,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Motivation: High-dimensional DNA methylation markers may mediate pathways linking environmental exposures with health outcomes. However, there is a lack of analytical methods to identify significant mediators for high-dimensional mediation analysis.<\/jats:p>\n               <jats:p>Results: Based on sure independent screening and minimax concave penalty techniques, we use a joint significance test for mediation effect. We demonstrate its practical performance using Monte Carlo simulation studies and apply this method to investigate the extent to which DNA methylation markers mediate the causal pathway from smoking to reduced lung function in the Normative Aging Study. We identify 2 CpGs with significant mediation effects.<\/jats:p>\n               <jats:p>Availability and implementation: R package, source code, and simulation study are available at https:\/\/github.com\/YinanZheng\/HIMA.<\/jats:p>\n               <jats:p>Contact: \u00a0lei.liu@northwestern.edu<\/jats:p>","DOI":"10.1093\/bioinformatics\/btw351","type":"journal-article","created":{"date-parts":[[2016,6,30]],"date-time":"2016-06-30T01:40:11Z","timestamp":1467250811000},"page":"3150-3154","source":"Crossref","is-referenced-by-count":181,"title":["Estimating and testing high-dimensional mediation effects in epigenetic studies"],"prefix":"10.1093","volume":"32","author":[{"given":"Haixiang","family":"Zhang","sequence":"first","affiliation":[{"name":"1 Center for Applied Mathematics, Tianjin University, Tianjin 300072, China"}]},{"given":"Yinan","family":"Zheng","sequence":"additional","affiliation":[{"name":"2 Department of Preventive Medicine"}]},{"given":"Zhou","family":"Zhang","sequence":"additional","affiliation":[{"name":"2 Department of Preventive Medicine"}]},{"given":"Tao","family":"Gao","sequence":"additional","affiliation":[{"name":"2 Department of Preventive Medicine"}]},{"given":"Brian","family":"Joyce","sequence":"additional","affiliation":[{"name":"2 Department of Preventive Medicine"}]},{"given":"Grace","family":"Yoon","sequence":"additional","affiliation":[{"name":"3 Department of Statistics, Northwestern University, Chicago, IL 60611, USA"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[{"name":"2 Department of Preventive Medicine"}]},{"given":"Joel","family":"Schwartz","sequence":"additional","affiliation":[{"name":"4 Department of Environmental Health, Harvard University, Boston, MA 02115, USA"}]},{"given":"Allan","family":"Just","sequence":"additional","affiliation":[{"name":"5 Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}]},{"given":"Elena","family":"Colicino","sequence":"additional","affiliation":[{"name":"4 Department of Environmental Health, Harvard University, Boston, MA 02115, USA"}]},{"given":"Pantel","family":"Vokonas","sequence":"additional","affiliation":[{"name":"6 Veterans Affairs Boston Healthcare System and Boston University School of Medicine, VA Normative Aging Study, Boston, MA 02118, USA"}]},{"given":"Lihui","family":"Zhao","sequence":"additional","affiliation":[{"name":"2 Department of Preventive Medicine"}]},{"given":"Jinchi","family":"Lv","sequence":"additional","affiliation":[{"name":"7 Data Sciences and Operations Department, University of Southern California, Los Angeles, CA 90089, USA"}]},{"given":"Andrea","family":"Baccarelli","sequence":"additional","affiliation":[{"name":"4 Department of Environmental Health, Harvard University, Boston, MA 02115, USA"}]},{"given":"Lifang","family":"Hou","sequence":"additional","affiliation":[{"name":"2 Department of Preventive Medicine"}]},{"given":"Lei","family":"Liu","sequence":"additional","affiliation":[{"name":"2 Department of Preventive Medicine"}]}],"member":"286","published-online":{"date-parts":[[2016,6,29]]},"reference":[{"key":"2023020113480203700_btw351-B1","doi-asserted-by":"crossref","first-page":"879","DOI":"10.1097\/EDE.0b013e31826c2bb9","article-title":"Mediation analysis for nonlinear models with confounding","volume":"23","author":"Albert","year":"2012","journal-title":"Epidemiology"},{"key":"2023020113480203700_btw351-B2","doi-asserted-by":"crossref","first-page":"599","DOI":"10.2217\/epi-2016-0001","article-title":"Tobacco smoking-associated genome-wide DNA methylation changes in the EPIC study","volume":"8","author":"Ambatipudi","year":"2016","journal-title":"Epigenomics"},{"key":"2023020113480203700_btw351-B30","doi-asserted-by":"crossref","first-page":"448","DOI":"10.4161\/epi.27584","article-title":"Air pollution and gene-specific methylation in the Normative Aging Study: association, effect modification, and mediation analysis","volume":"9","author":"Bind","year":"2014","journal-title":"Epigenetics"},{"key":"2023020113480203700_btw351-B3","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1093\/bioinformatics\/btt633","article-title":"Testing multiple biological mediators simultaneously","volume":"30","author":"Boca","year":"2014","journal-title":"Bioinformatics"},{"key":"2023020113480203700_btw351-B4","doi-asserted-by":"crossref","first-page":"232","DOI":"10.1214\/10-AOAS388","article-title":"Coordinate descent algorithms for nonconvex penalized regression, with applications to biological feature selection","volume":"5","author":"Breheny","year":"2011","journal-title":"Ann. 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