Testing Mediation Effects in High-Dimensional Epigenetic Studies

Yuzhao Gao, Haitao Yang, Ruiling Fang, Yanbo Zhang, Ellen L. Goode, Yuehua Cui

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Mediation analysis has been a powerful tool to identify factors mediating the association between exposure variables and outcomes. It has been applied to various genomic applications with the hope to gain novel insights into the underlying mechanism of various diseases. Given the high-dimensional nature of epigenetic data, recent effort on epigenetic mediation analysis is to first reduce the data dimension by applying high-dimensional variable selection techniques, then conducting testing in a low dimensional setup. In this paper, we propose to assess the mediation effect by adopting a high-dimensional testing procedure which can produce unbiased estimates of the regression coefficients and can properly handle correlations between variables. When the data dimension is ultra-high, we first reduce the data dimension from ultra-high to high by adopting a sure independence screening (SIS) method. We apply the method to two high-dimensional epigenetic studies: one is to assess how DNA methylations mediate the association between alcohol consumption and epithelial ovarian cancer (EOC) status; the other one is to assess how methylation signatures mediate the association between childhood maltreatment and post-traumatic stress disorder (PTSD) in adulthood. We compare the performance of the method with its counterpart via simulation studies. Our method can be applied to other high-dimensional mediation studies where high-dimensional mediation variables are collected.

Original languageEnglish (US)
Article number1195
JournalFrontiers in Genetics
Volume10
DOIs
StatePublished - Nov 22 2019

Keywords

  • DNA methylation
  • de-sparsify
  • high-dimensional mediation
  • high-dimensional testing
  • mediation analysis

ASJC Scopus subject areas

  • Molecular Medicine
  • Genetics
  • Genetics(clinical)

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