HIMA2: high-dimensional mediation analysis and its application in epigenome-wide DNA methylation data

Chamila Perera, Haixiang Zhang, Yinan Zheng, Lifang Hou, Annie Qu, Cheng Zheng, Ke Xie, Lei Liu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

11 Scopus citations


Mediation analysis plays a major role in identifying significant mediators in the pathway between environmental exposures and health outcomes. With advanced data collection technology for large-scale studies, there has been growing research interest in developing methodology for high-dimensional mediation analysis. In this paper we present HIMA2, an extension of the HIMA method (Zhang in Bioinformatics 32:3150–3154, 2016). First, the proposed HIMA2 reduces the dimension of mediators to a manageable level based on the sure independence screening (SIS) method (Fan in J R Stat Soc Ser B 70:849–911, 2008). Second, a de-biased Lasso procedure is implemented for estimating regression parameters. Third, we use a multiple-testing procedure to accurately control the false discovery rate (FDR) when testing high-dimensional mediation hypotheses. We demonstrate its practical performance using Monte Carlo simulation studies and apply our method to identify DNA methylation markers which mediate the pathway from smoking to reduced lung function in the Coronary Artery Risk Development in Young Adults (CARDIA) Study.

Original languageEnglish (US)
Article number296
JournalBMC bioinformatics
Issue number1
StatePublished - Dec 2022


  • Causality
  • Epigenetics
  • Joint significant test
  • Variable selection

ASJC Scopus subject areas

  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Computer Science Applications
  • Applied Mathematics


Dive into the research topics of 'HIMA2: high-dimensional mediation analysis and its application in epigenome-wide DNA methylation data'. Together they form a unique fingerprint.

Cite this