Mediation effect selection in high-dimensional and compositional microbiome data

Stat Med. 2021 Feb 20;40(4):885-896. doi: 10.1002/sim.8808. Epub 2020 Nov 17.

Abstract

The microbiome plays an important role in human health by mediating the path from environmental exposures to health outcomes. The relative abundances of the high-dimensional microbiome data have an unit-sum restriction, rendering standard statistical methods in the Euclidean space invalid. To address this problem, we use the isometric log-ratio transformations of the relative abundances as the mediator variables. To select significant mediators, we consider a closed testing-based selection procedure with desirable confidence. Simulations are provided to verify the effectiveness of our method. As an illustrative example, we apply the proposed method to study the mediation effects of murine gut microbiome between subtherapeutic antibiotic treatment and body weight gain, and identify Coprobacillus and Adlercreutzia as two significant mediators.

Keywords: closed testing; compositional microbiome data; high-dimensional data; isometric log-ratio transformation; mediation analysis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Humans
  • Mice
  • Microbiota*
  • Research Design