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Mediation analysis in a case-control study when the mediator is a censored variable.

Jian Wang1, Jing Ning1, Sanjay Shete1,2

  • 1Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, Texas.

Statistics in Medicine
|November 14, 2018
PubMed
Summary

This study introduces MAC-CC, a new method for mediation analysis with censored mediators in case-control studies. The method accurately estimates effects, finding no mediation by age at menopause for type 2 diabetes risk.

Keywords:
case-control studycensored mediatorindirect effectsmediation analysissemiparametric accelerated failure time model

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Area of Science:

  • Biostatistics
  • Epidemiology
  • Statistical Genetics

Background:

  • Mediation analysis assesses direct and indirect effects of variables.
  • Censored mediators (e.g., age at menopause) and binary outcomes (e.g., type 2 diabetes) present analytical challenges.
  • Case-control study data can bias standard mediation analysis.

Purpose of the Study:

  • To propose a novel approach (MAC-CC) for mediation analysis with censored mediators using case-control data.
  • To adapt counterfactual definitions for assessing indirect and direct effects.
  • To evaluate the performance of MAC-CC against existing methods.

Main Methods:

  • Developed the MAC-CC approach using a semiparametric accelerated failure time model and a pseudo-likelihood function.
  • Adapted counterfactual definitions for indirect and direct effect measures.
  • Conducted simulation studies and applied the method to a real-world case-control study.

Main Results:

  • MAC-CC accurately estimates path coefficients, indirect effects, and mediated proportions.
  • Simulations demonstrated MAC-CC's superior performance compared to naive and complete-case approaches.
  • Analysis of genetic variants, age at menopause, and type 2 diabetes revealed no significant mediation.

Conclusions:

  • The MAC-CC approach provides accurate mediation analysis for censored mediators in case-control studies.
  • Age at menopause does not mediate the association between genetic variants and type 2 diabetes in the studied population.