Skills

Bio Causal Genomics Mediation Analysis

Decompose genetic effects into direct and indirect paths through mediating variables...

Install

npx skills add FreedomIntelligence/OpenClaw-Medical-Skills --skill bio-causal-genomics-mediation-analysis -g -a claude-code -y
Category
Testing
Updated
4mo ago
License
See repository
Context cost
Mediumabout 2,330 tokens
Runs scripts
No, instructions only

What it does

Decompose genetic effects into direct and indirect paths through mediating variables using the mediation R package. Tests whether gene expression, methylation, or other molecular phenotypes mediate the effect of genetic variants on disease. Use when testing whether a molecular phenotype mediates the genotype-to-phenotype relationship.

Version Compatibility

Reference examples tested with: R stats (base), ggplot2 3.5+

Before using code patterns, verify installed versions match. If versions differ:

  • R: packageVersion('<pkg>') then ?function_name to verify parameters

If code throws ImportError, AttributeError, or TypeError, introspect the installed package and adapt the example to match the actual API rather than retrying.

Mediation Analysis

"Test whether gene expression mediates the effect of this variant on disease" → Decompose the total genetic effect into direct and indirect (mediated) paths through a molecular phenotype, estimating ACME, ADE, and proportion mediated with bootstrap confidence intervals.

  • R: mediation::mediate() for causal mediation analysis

Framework

Causal mediation decomposes the total effect of a treatment (genotype) on an outcome (phenotype) into:

  • ACME (Average Causal Mediation Effect) - Indirect effect through the mediator
  • ADE (Average Direct Effect) - Direct effect not through the mediator
  • Total effect = ACME + ADE
  • Proportion mediated = ACME / Total effect

Typical genomic applications:

  • SNP -> gene expression (mediator) -> disease
  • SNP -> DNA methylation (mediator) -> gene expression
  • SNP -> protein levels (mediator) -> clinical outcome

Basic Mediation with the mediation Package

Goal: Decompose a genetic effect into direct and indirect (mediated) paths through a molecular phenotype.

Approach: Fit separate models for mediator and outcome, then run mediate() with bootstrap to estimate ACME (indirect), ADE (direct), and proportion mediated.

library(mediation)

# --- Step 1: Fit mediator model ---
# How does the treatment (genotype) affect the mediator (expression)?
mediator_model <- lm(expression ~ genotype + age + sex + pc1 + pc2, data = dat)
Read the whole SKILL.md on GitHub

More in Testing