ArticlemedRxiv : the preprint server for health sciences2023
Methods for Mediation Analysis with High-Dimensional DNA Methylation Data: Possible Choices and Comparison.
Dylan Clark-Boucher, Xiang Zhou, Jiacong Du, Yongmei Liu, Belinda L Needham, Jennifer A Smith, Bhramar Mukherjee
Abstract readPreprint
In one paragraphArticle in medRxiv : the preprint server for health sciences, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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2 · The registryThe trial behind it
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4 · The recordCorrections and comments
5 · Who and what moneyAuthors and funding
7 authors.
Dylan Clark-BoucherDepartment of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA.
Xiang ZhouDepartment of Biostatistics, University of Michigan, Ann Arbor, MI.
Jiacong DuDepartment of Biostatistics, University of Michigan, Ann Arbor, MI.
Yongmei LiuDepartment of Medicine, Divisions of Cardiology and Neurology, Duke University Medical Center, Durham, NC.
Belinda L NeedhamDepartment of Epidemiology, University of Michigan, Ann Arbor, MI.
Jennifer A SmithDepartment of Epidemiology, University of Michigan, Ann Arbor, MI.
Bhramar MukherjeeDepartment of Biostatistics, University of Michigan, Ann Arbor, MI.
Funding
UCLA Clinical Translational Science InstituteUL1TR001881 · NCATS · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI ARLEEN F. BROWN, ARASH NAEIM · 2016 to 2026
$118.1MInstitute for Clinical and Translational ResearchUL1TR001079 · NCATS · JOHNS HOPKINS UNIVERSITY · PI FORD, DANIEL ERNEST · 2013 to 2017
$60.1MTransgenic & Knock-out MouseP30DK063491 · NIDDK · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI MILES Frome WILKINSON · 2003 to 2026
$40.4MWake Forest Clinical and Translational Science AwardUL1TR001420 · NCATS · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI ARD, JAMY D, FOLEY, KRISTIE L · 2015 to 2023
$32.3MClinical and Translational Science AwardUL1TR000040 · NCATS · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI GINSBERG, HENRY N · 2012 to 2015
$26.2MTask Area A Core Study Operations.Task Area A shall encompass annual follow-up of cohort members, clinical endpoints ascertainment, study coordination activities, maintenance of the database and biosp75N92020D00001 · NHLBI · UNIVERSITY OF WASHINGTON · PI MCCLELLAND, ROBYN LEAGH · 2020 to 2025
$17.2MA Longitudinal Epigenetic Study of AtherosclerosisR01HL135009 · NHLBI · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI LIU, YONGMEI · 2017 to 2020
$5.8MTask Area A shall encompass annual follow-up of cohort members, clinical events investigations, study operations, and data analysis and manuscript writing. If implemented, Task A.1 will provide fundin75N92020D00005 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI WATSON, KAROL E · 2020 to 2025
$5.1MTO EXERCISE OPTION PERIOD ONE (1) FOR TASK AREA A - MESA CORE OPERATIONS, FIELD CENTER.75N92020D00004 · NHLBI · NORTHWESTERN UNIVERSITY · PI SIEGEL, JONATHAN H · 2020 to 2025
$4.5MTask Area A shall encompass annual follow-up of cohort members, clinical events investigations, study operations, and data analysis and manuscript writing. If implemented, Task A.1 will provide fundin75N92020D00006 · NHLBI · UNIVERSITY OF MINNESOTA · PI PANKOW, JAMES S · 2020 to 2025
$4.4MCell-specific genomic features of Alzheimer's disease progressionRF1AG054474 · NIA · WAKE FOREST UNIVERSITY HEALTH SCIENCES · PI DING, JINGZHONG, LIU, YONGMEI · 2017 to 2019
$4.1MTask Area A shall encompass annual follow-up of cohort members, clinical events investigations, study operations, and data analysis and manuscript writing. If implemented, Task A.1 will provide fundin75N92020D00003 · NHLBI · JOHNS HOPKINS UNIVERSITY · PI POST, WENDY S · 2020 to 2025
$3.8MNCATS NIH HHS UL1 TR000040NCATS NIH HHS UL1 TR001079NCATS NIH HHS UL1 TR001420NCATS NIH HHS UL1 TR001881NCI NIH HHS UG3 CA267907NHGRI NIH HHS R01 HG008773NHLBI NIH HHS 75N92020D00001NHLBI NIH HHS 75N92020D00002NHLBI NIH HHS 75N92020D00003NHLBI NIH HHS 75N92020D00004NHLBI NIH HHS 75N92020D00005NHLBI NIH HHS 75N92020D00006NHLBI NIH HHS 75N92020D00007NHLBI NIH HHS HHSN268201500003CNHLBI NIH HHS HHSN268201500003INHLBI NIH HHS N01 HC095159NHLBI NIH HHS N01 HC095160NHLBI NIH HHS N01 HC095161NHLBI NIH HHS N01 HC095162NHLBI NIH HHS N01 HC095163NHLBI NIH HHS N01 HC095164NHLBI NIH HHS N01 HC095165NHLBI NIH HHS N01 HC095166NHLBI NIH HHS N01 HC095167NHLBI NIH HHS N01 HC095168NHLBI NIH HHS N01 HC095169NHLBI NIH HHS R01 HL101250NHLBI NIH HHS R01 HL126477NHLBI NIH HHS R01 HL135009NHLBI NIH HHS R01 HL141292NIA NIH HHS RF1 AG054474NIDDK NIH HHS P30 DK063491NIDDK NIH HHS R01 DK101921
6 · The paper itselfAbstract
Epigenetic researchers often evaluate DNA methylation as a mediator between social/environmental exposures and disease, but modern statistical methods for jointly evaluating many mediators have not been widely adopted. We compare seven methods for high-dimensional mediation analysis with continuous outcomes through both diverse simulations and analysis of DNAm data from a large national cohort in the United States, while providing an R package for their implementation. Among the considered choices, the best-performing methods for detecting active mediators in simulations are the Bayesian sparse linear mixed model by Song et al. (2020) and high-dimensional mediation analysis by Gao et al. (2019); while the superior methods for estimating the global mediation effect are high-dimensional linear mediation analysis by Zhou et al. (2021) and principal component mediation analysis by Huang and Pan (2016). We provide guidelines for epigenetic researchers on choosing the best method in practice and offer suggestions for future methodological development.
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PMID36824903
PMCPMC9949196
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