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In this work, we formulate a multiple-hypothesis testing framework for mediator selection from a high-dimensional candidate set, and propose a method, which extends the recent development in false discovery rate (FDR)-controlled variable selection with knockoff to select mediators with FDR control. We show that the proposed method and algorithm achieved finite sample FDR control. We present extensive simulation results to demonstrate the power and finite sample performance compared with the existing method. Lastly, we demonstrate the method for analyzing the Adolescent Brain Cognitive Development (ABCD) study, in which the proposed method selects several resting-state functional magnetic resonance imaging connectivity markers as mediators for the relationship between adverse childhood events and the crystallized composite score in the NIH toolbox.<\/jats:p>","DOI":"10.1093\/biomtc\/ujae064","type":"journal-article","created":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T23:26:34Z","timestamp":1722295594000},"source":"Crossref","is-referenced-by-count":3,"title":["Controlling false discovery rate for mediator selection in high-dimensional data"],"prefix":"10.1093","volume":"80","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3732-2789","authenticated-orcid":false,"given":"Ran","family":"Dai","sequence":"first","affiliation":[{"name":"Department of Biostatistics, University of Nebraska Medical Center , Omaha, NE 68198 , United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruiyang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Columbia University , New York , NY 10032 , United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3177-6357","authenticated-orcid":false,"given":"Seonjoo","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Columbia University , New York, NY 10032 , United States"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0214-6479","authenticated-orcid":false,"given":"Ying","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Columbia University , New York, NY 10032 , United States"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,7,29]]},"reference":[{"issue":"9","key":"2024072915095978100_bib1","doi-asserted-by":"crossref","first-page":"S359","DOI":"10.1016\/j.biopsych.2021.02.895","article-title":"Internalizing symptoms and adverse childhood experiences associated with functional connectivity in a middle childhood sample","volume":"89","author":"Albertina","year":"2021","journal-title":"Biological Psychiatry: Cognitive Neuroscience and Neuroimaging"},{"key":"2024072915095978100_bib2","doi-asserted-by":"crossref","first-page":"2055","DOI":"10.1214\/15-AOS1337","article-title":"Controlling the false discovery rate via knockoffs","volume":"43","author":"Barber","year":"2015","journal-title":"The Annals of Statistics"},{"key":"2024072915095978100_bib3","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1214\/19-AOS1852","article-title":"Robust inference with knockoffs","volume":"48","author":"Barber","year":"2020","journal-title":"The Annals of Statistics"},{"key":"2024072915095978100_bib4","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.jaac.2017.12.011","article-title":"Early childhood adverse experiences, inferior frontal gyrus connectivity, and the trajectory of externalizing psychopathology","volume":"57","author":"Barch","year":"2018","journal-title":"Journal of the American Academy of Child & Adolescent Psychiatry"},{"key":"2024072915095978100_bib5","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":"Journal of Personality and Social Psychology"},{"issue":"535","key":"2024072915095978100_bib6","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1080\/01621459.2020.1729163","article-title":"Metropolized knockoff sampling","volume":"116","author":"Bates","year":"2020","journal-title":"Journal of the American Statistical Association"},{"key":"2024072915095978100_bib7","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: A practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"Journal of the Royal Statistical Society. 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