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Unal Mutlu1, Mohammad Arfan Ikram1, Mohammad Kamran Ikram1,2

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International Journal of Epidemiology
|December 4, 2018
PubMed
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Negative mediated interaction in causal analysis can be challenging to interpret. This study proposes a biological interpretation for negative mediated interaction, highlighting its relevance in biological and biochemical processes.

Keywords:
biologycausal inferenceclinical medicinefour-way decompositioninteractionmediation

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Area of Science:

  • Causal Inference
  • Biostatistics
  • Epidemiology

Background:

  • Causal mediation analysis decomposes total effects into four components: mediation only, interaction only, mediated interaction, and neither.
  • Interpreting effect sizes is difficult when these components have opposing signs.
  • Negative mediated interaction lacks intuitive biological or mechanical interpretation.

Purpose of the Study:

  • To propose an interpretation for negative mediated interaction using biological examples.
  • To aid researchers in recognizing negative effect estimates as potentially relevant biological processes.

Main Methods:

  • Focus on negative mediated interaction within a counterfactual framework.
  • Define conditions for negative mediated interaction: opposing directions of interaction effect on outcome and exposure effect on mediator.

Main Results:

  • Biological examples illustrating negative mediated interaction are provided.
  • Examples include drug treatment, enzyme allosteric effects, cardiovascular adaptations, and antibiotic interactions.

Conclusions:

  • Negative mediated interaction can be conceptually understood through biological mechanisms.
  • Researchers should consider negative effect estimates as potentially significant biological findings.