title: Estimating and testing high-dimensional mediation effects in epigenetic studies.
abstract: 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.
  
  
  
  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.
  
  
  
  R package, source code, and simulation study are available at https://github.com/YinanZheng/HIMA CONTACT: lei.liu@northwestern.edu.
authors.affiliation: Center for Applied Mathematics, Tianjin University, Tianjin 300072, China.
authors.forename: Haixiang
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Preventive Medicine.
authors.forename: Yinan
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Department of Preventive Medicine.
authors.forename: Zhou
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Preventive Medicine.
authors.forename: Tao
authors.initials: T
authors.lastname: Gao
authors.affiliation: Department of Preventive Medicine.
authors.forename: Brian
authors.initials: B
authors.lastname: Joyce
authors.affiliation: Department of Statistics, Northwestern University, Chicago, IL 60611, USA.
authors.forename: Grace
authors.initials: G
authors.lastname: Yoon
authors.affiliation: Department of Preventive Medicine.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Environmental Health, Harvard University, Boston, MA 02115, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Schwartz
authors.affiliation: Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Allan
authors.initials: A
authors.lastname: Just
authors.affiliation: Department of Environmental Health, Harvard University, Boston, MA 02115, USA.
authors.forename: Elena
authors.initials: E
authors.lastname: Colicino
authors.affiliation: Veterans Affairs Boston Healthcare System and Boston University School of Medicine, VA Normative Aging Study, Boston, MA 02118, USA.
authors.forename: Pantel
authors.initials: P
authors.lastname: Vokonas
authors.affiliation: Department of Preventive Medicine.
authors.forename: Lihui
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Data Sciences and Operations Department, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Jinchi
authors.initials: J
authors.lastname: Lv
authors.affiliation: Department of Environmental Health, Harvard University, Boston, MA 02115, USA.
authors.forename: Andrea
authors.initials: A
authors.lastname: Baccarelli
authors.affiliation: Department of Preventive Medicine.
authors.forename: Lifang
authors.initials: L
authors.lastname: Hou
authors.affiliation: Department of Preventive Medicine.
authors.forename: Lei
authors.initials: L
authors.lastname: Liu
mesh_terms: D000375:Aging; D019175:DNA Methylation; D057890:Epigenomics; D006801:Humans; D009010:Monte Carlo Method; D012907:Smoking