Mediation

This page is a placeholder for the detailed mediation guide. The section is included in the association guide now because mediation is a distinct scientific question, not a variant of ordinary regression.

Question

Use mediation when the question is:

Is the association between exposure X and outcome Y transmitted through mediator M?

For example:

Is the association between an AD PRS and dementia mediated through Braak stage?

Intended Pattern

med <- associate$mediation(
  data,
  exposure = PRS_AD,
  mediator = braaksc,
  outcome = demented,
  covariates = c(age, sex, PCA)
)

The exposure is the variable whose effect is being decomposed. The mediator is the intermediate variable. The outcome is the final phenotype or endpoint.

What Mediation Is Not

Mediation is different from interaction:

Question	Workflow
Does the PRS effect differ by sex?	heterogeneity / interaction
Is the PRS effect partly transmitted through pathology?	mediation
Is PRS associated with pathology?	direct regression association
Does pathology improve prediction?	evaluation or nested comparison

Returned Object

Mediation results should return a PolyGeniusAssociations object with a mediation-specific summary schema.

Schema

Column	Meaning
method	Mediation method used.
outcome, exposure, mediator	Variables defining the mediation pathway.
effect, effect.type	Reported effect and high-level type, such as total, direct, indirect, or proportion.mediated.
estimate, se, lower, upper	Estimated effect and uncertainty on the method-specific scale.
statistic, p.value, adj.p.value	Inference for the effect row.
n, fit.id	Analysis sample size and artifact/diagnostic key.

Added Artifacts

Mediation artifacts are reserved for richer decomposition output, fitted component models, and diagnostics that do not fit into the summary table.

Plotting

Mediation outputs are naturally shown as:

• effect-decomposition tables;
• forest plots of total, direct, and indirect effects;
• pathway diagrams when the object contains enough information.

The detailed plotting guidance will be added with the full mediation workflow.

Status

The mediation guide is under construction. The page is present so users can see where mediation fits in the broader association question map.