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Third-variable effect analysis with multilevel additive models.

Qingzhao YuBin Li
Published in: PloS one (2020)
Third-variable effect refers to the effect transmitted by third-variables that intervene in the relationship between an exposure and a response variable. Third-variable effect analysis has been broadly studied in many fields. However, it remains a challenge for researchers to differentiate indirect effect of individual factor from multiple third-variables, especially when the involving variables are of hierarchical structure. Yu et al. (2014) defined third-variable effects that were consistent for all different types of response (categorical or continuous), exposure, or third-variables. With these definitions, multiple third-variables can be considered simultaneously, and the indirect effects carried by individual third-variables can be separated from the total effect. In this paper, we extend the definitions of third-variable effects to multilevel data structures, where multilevel additive models are adapted to model the variable relationships. And then third-variable effects can be estimated at different levels. Moreover, transformations on variables are allowed to present nonlinear relationships among variables. We compile an R package mlma, to carry out the proposed multilevel third-variable analysis. Simulations show that the proposed method can effectively differentiate and estimate third-variable effects from different levels. Further, we implement the method to explore the racial disparity in body mass index accounting for both environmental and individual level risk factors.
Keyphrases
  • body mass index
  • risk factors
  • physical activity
  • mass spectrometry
  • risk assessment
  • high resolution
  • machine learning
  • deep learning