Please identify a quantitative research article evaluating mediation in your field and provide the citation.
Air pollution and gene-specific methylation in the Normative Aging Study
What is the primary discipline of the authors?
Environmental Health, Harvard
Marie-abele Bind*,
Johanna Lepeule,
Antonella Zanobetti,
andrea Baccarelli,
Petros Koutrakis,
Joel Schwartz
Brent Coull*,
* + Biostatistics, Harvard
Antonio Gasparrini, Medical Statistics, London HTM
Letizia Tarantini, Molecular and Genetic Epidemiology, U of Milan
Pantel Vokonas, VA Boston Healthcare System
Draw a DAG representing the implicit or explicit causal model explored in this paper (you do not need to post your DAG, but we will try to discuss in class).
What is the exposure of interest?
Air pollution
What is the outcome of interest?
Cardiovascular-related biomarkers (inflammatory and coagulation markers)
What is the hypothesized mediator of interest and how is it measured?
Gene-specific methylation
Describe the modeling approach and briefly report the estimated total, direct, and indirect effects (if these are reported).
Investigators fitted two linear mixed-effects models to determine the mediated effect of air pollution on cardiovascular-related biomarkers through a change in gene-specific methylation:
The effect of mediation was reported as the standard deviation increase from the mean. It is given by the product formula .
If the direct effect is reported, would you describe this as a natural direct effect, a controlled direct effect, or something else?
I think this is a natural direct effect because we are not fixing the mediator to some value (that would be a controlled direct effect).
Do you think there is potential measurement error in the mediator and how would that affect the results?
The participant’s blood sample was collected at every visit and DNA was isolated to assess gene-specific DNA methylation using highly quantitative methods based on bisulfite PCR pyrosequencing. Measurement error in this process was probably pretty minimal.
Do you think there are unmeasured confounders of the mediator-outcome association and how would that affect the results of the mediation analysis?
An unmeasured confounder of the mediator-outcome association would have to affect gene-specific methylation and coagulation and inflammation factors. I cannot come up with other confounders, but I do think there may be some residual confounding because race, BMI, and smoking status are imperfect measures.
Do you have any critiques of the paper?
Maybe stating more specifically the type of mediation analysis (the controlled direct effect of natural direct effect)?