{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,18]],"date-time":"2025-11-18T03:33:32Z","timestamp":1763436812865,"version":"3.41.2"},"reference-count":24,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2024,1,30]],"date-time":"2024-01-30T00:00:00Z","timestamp":1706572800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R21 AG063370","R21 AG068955","R01 AG081244","UL1 TR002345"],"award-info":[{"award-number":["R21 AG063370","R21 AG068955","R01 AG081244","UL1 TR002345"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Motivation<\/jats:title>\n                  <jats:p>There has been substantial recent interest in developing methodology for high-dimensional mediation analysis. Yet, the majority of mediation statistical methods lean heavily on mean regression, which limits their ability to fully capture the complex mediating effects across the outcome distribution. To bridge this gap, we propose a novel approach for selecting and testing mediators throughout the full range of the outcome distribution spectrum.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The proposed high-dimensional quantile mediation model provides a comprehensive insight into how potential mediators impact outcomes via their mediation pathways. This method\u2019s efficacy is demonstrated through extensive simulations. The study presents a real-world data application examining the mediating effects of DNA methylation on the relationship between maternal smoking and offspring birthweight.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Availability and implementation<\/jats:title>\n                  <jats:p>Our method offers a publicly available and user-friendly function qHIMA(), which can be accessed through the R package HIMA at https:\/\/CRAN.R-project.org\/package=HIMA.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/bioinformatics\/btae055","type":"journal-article","created":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T02:04:44Z","timestamp":1706666684000},"source":"Crossref","is-referenced-by-count":4,"title":["High-dimensional quantile mediation analysis with application to a birth cohort study of mother\u2013newborn pairs"],"prefix":"10.1093","volume":"40","author":[{"given":"Haixiang","family":"Zhang","sequence":"first","affiliation":[{"name":"Center for Applied Mathematics, Tianjin University , Tianjin 300072, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3992-1918","authenticated-orcid":false,"given":"Xiumei","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Population, Family and Reproductive Health, Center On the Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health , Baltimore, MD 21205, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2006-7320","authenticated-orcid":false,"given":"Yinan","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, Northwestern University , Chicago, IL 60611, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lifang","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, Northwestern University , Chicago, IL 60611, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4451-302X","authenticated-orcid":false,"given":"Xiaobin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Population, Family and Reproductive Health, Center On the Early Life Origins of Disease, Johns Hopkins University Bloomberg School of Public Health , Baltimore, MD 21205, United States"},{"name":"Department of Pediatrics, Johns Hopkins University School of Medicine , Baltimore, MD 21205, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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, United States"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,1,30]]},"reference":[{"key":"2024021711542771900_btae055-B1","doi-asserted-by":"crossref","first-page":"4182","DOI":"10.1002\/sim.7423","article-title":"Quantile causal mediation analysis allowing longitudinal data","volume":"36","author":"Bind","year":"2017","journal-title":"Stat Med"},{"key":"2024021711542771900_btae055-B2","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1080\/01621459.2020.1765785","article-title":"A multiple-testing procedure for high-dimensional mediation hypotheses","volume":"117","author":"Dai","year":"2022","journal-title":"J Am Stat Assoc"},{"key":"2024021711542771900_btae055-B3","doi-asserted-by":"crossref","first-page":"3346","DOI":"10.1002\/sim.8199","article-title":"Global test for high-dimensional mediation: testing groups of potential mediators","volume":"38","author":"Djordjilovi\u0107","year":"2019","journal-title":"Stat Med"},{"key":"2024021711542771900_btae055-B4","doi-asserted-by":"crossref","DOI":"10.1093\/bib\/bbaa113","article-title":"Gene-based mediation analysis in epigenetic studies","volume":"22","author":"Fang","year":"2021","journal-title":"Brief Bioinform"},{"key":"2024021711542771900_btae055-B5","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1186\/s12885-020-07407-x","article-title":"Ahrr methylation in heavy smokers: associations with smoking, lung cancer risk, and lung cancer mortality","volume":"20","author":"Grieshober","year":"2020","journal-title":"BMC Cancer"},{"year":"2023","author":"Li","key":"2024021711542771900_btae055-B6"},{"key":"2024021711542771900_btae055-B7","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1080\/01621459.2021.1914634","article-title":"Large-scale hypothesis testing for causal mediation effects with applications in genome-wide epigenetic studies","volume":"117","author":"Liu","year":"2022","journal-title":"J Am Stat Assoc"},{"key":"2024021711542771900_btae055-B8","doi-asserted-by":"crossref","first-page":"e1007768","DOI":"10.1371\/journal.pcbi.1007768","article-title":"High-dimensional mediation analysis in survival models","volume":"16","author":"Luo","year":"2020","journal-title":"PLoS Comput Biol"},{"key":"2024021711542771900_btae055-B9","first-page":"e00011","article-title":"Boston birth cohort profile: rationale and study design","volume":"1","author":"Pearson","year":"2022","journal-title":"Precis Nutr"},{"key":"2024021711542771900_btae055-B10","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1186\/s12859-022-04748-1","article-title":"HIMA2: high-dimensional mediation analysis and its application in epigenome-wide DNA methylation data","volume":"23","author":"Perera","year":"2022","journal-title":"BMC Bioinformatics"},{"key":"2024021711542771900_btae055-B11","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1080\/00273171.2014.904221","article-title":"Quantile mediation models: a comparison of methods for assessing mediation across the outcome distribution","volume":"49","author":"Shen","year":"2014","journal-title":"Multivariate Behav Res"},{"key":"2024021711542771900_btae055-B12","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1214\/18-AOAS1210","article-title":"Compositional mediation analysis for microbiome studies","volume":"13","author":"Sohn","year":"2019","journal-title":"Ann Appl Stat"},{"key":"2024021711542771900_btae055-B13","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1111\/rssb.12485","article-title":"High-dimensional quantile regression: convolution smoothing and concave regularization","volume":"84","author":"Tan","year":"2022","journal-title":"J R Stat Soc Ser B"},{"key":"2024021711542771900_btae055-B14","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1186\/s13148-020-00908-3","article-title":"AHRR cg05575921 methylation in relation to smoking and pm2.5 exposure among Taiwanese men and women","volume":"12","author":"Tantoh","year":"2020","journal-title":"Clin Epigenetics"},{"key":"2024021711542771900_btae055-B15","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1093\/bioinformatics\/btz565","article-title":"Estimating and testing the microbial causal mediation effect with high-dimensional and compositional microbiome data","volume":"36","author":"Wang","year":"2020","journal-title":"Bioinformatics"},{"key":"2024021711542771900_btae055-B16","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1001\/jama.287.2.195","article-title":"Maternal cigarette smoking, metabolic gene polymorphism, and infant birth weight","volume":"287","author":"Wang","year":"2002","journal-title":"JAMA"},{"key":"2024021711542771900_btae055-B17","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1186\/s13148-021-01032-6","article-title":"DNA methylation mediates the effect of maternal smoking on offspring birthweight: a birth cohort study of multi-ethnic us mother\u2013newborn pairs","volume":"13","author":"Xu","year":"2021","journal-title":"Clin Epigenetics"},{"key":"2024021711542771900_btae055-B18","doi-asserted-by":"crossref","first-page":"3209","DOI":"10.1016\/j.csbj.2021.05.042","article-title":"Statistical methods for mediation analysis in the era of high-throughput genomics: current successes and future challenges","volume":"19","author":"Zeng","year":"2021","journal-title":"Comput Struct Biotechnol J"},{"key":"2024021711542771900_btae055-B19","doi-asserted-by":"crossref","first-page":"894","DOI":"10.1214\/09-AOS729","article-title":"Nearly unbiased variable selection under minimax concave penalty","volume":"38","author":"Zhang","year":"2010","journal-title":"Ann Stat"},{"key":"2024021711542771900_btae055-B20","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1002\/sim.8808","article-title":"Mediation effect selection in high-dimensional and compositional microbiome data","volume":"40","author":"Zhang","year":"2021","journal-title":"Stat Med"},{"key":"2024021711542771900_btae055-B21","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s12561-019-09253-3","article-title":"Testing for mediation effect with application to human microbiome data","volume":"13","author":"Zhang","year":"2021","journal-title":"Stat Biosci"},{"volume-title":"Epigenome-Wide Association Studies: Methods and Protocols 2432","year":"2022","author":"Zhang","key":"2024021711542771900_btae055-B22"},{"key":"2024021711542771900_btae055-B23","doi-asserted-by":"crossref","first-page":"3815","DOI":"10.1093\/bioinformatics\/btab564","article-title":"Mediation analysis for survival data with high-dimensional mediators","volume":"37","author":"Zhang","year":"2021","journal-title":"Bioinformatics"},{"key":"2024021711542771900_btae055-B24","doi-asserted-by":"crossref","first-page":"3150","DOI":"10.1093\/bioinformatics\/btw351","article-title":"Estimating and testing high-dimensional mediation effects in epigenetic studies","volume":"32","author":"Zhang","year":"2016","journal-title":"Bioinformatics"}],"container-title":["Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/bioinformatics\/advance-article-pdf\/doi\/10.1093\/bioinformatics\/btae055\/56485333\/btae055.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/40\/2\/btae055\/56696329\/btae055.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article-pdf\/40\/2\/btae055\/56696329\/btae055.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,17]],"date-time":"2024-02-17T11:55:01Z","timestamp":1708170901000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/bioinformatics\/article\/doi\/10.1093\/bioinformatics\/btae055\/7593745"}},"subtitle":[],"editor":[{"given":"Russell","family":"Schwartz","sequence":"additional","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2024,1,30]]},"references-count":24,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2024,2,1]]}},"URL":"https:\/\/doi.org\/10.1093\/bioinformatics\/btae055","relation":{},"ISSN":["1367-4803","1367-4811"],"issn-type":[{"type":"print","value":"1367-4803"},{"type":"electronic","value":"1367-4811"}],"subject":[],"published-other":{"date-parts":[[2024,2,1]]},"published":{"date-parts":[[2024,1,30]]},"article-number":"btae055"}}