# Bio Causal Genomics Pleiotropy Detection

Detect and correct for horizontal pleiotropy in Mendelian randomization analyses using...

- Repository: https://github.com/FreedomIntelligence/OpenClaw-Medical-Skills (3090 stars)
- Category: Engineering
- License: see repository
- Last updated: 2026-07-21
- Runs scripts: no, instructions only

## Install

Claude Code: `npx skills add FreedomIntelligence/OpenClaw-Medical-Skills --skill bio-causal-genomics-pleiotropy-detection -g -a claude-code -y`
Codex: `npx skills add FreedomIntelligence/OpenClaw-Medical-Skills --skill bio-causal-genomics-pleiotropy-detection -g -a codex -y`
Cursor: `npx skills add FreedomIntelligence/OpenClaw-Medical-Skills --skill bio-causal-genomics-pleiotropy-detection -g -a cursor -y`
Gemini CLI: `npx skills add FreedomIntelligence/OpenClaw-Medical-Skills --skill bio-causal-genomics-pleiotropy-detection -g -a gemini-cli -y`

## Description

Detect and correct for horizontal pleiotropy in Mendelian randomization analyses using MR-PRESSO for outlier removal, MR-Egger regression for directional pleiotropy, and Steiger filtering for variant directionality. Use when validating MR results, detecting pleiotropic instruments, or running sensitivity analyses for causal inference.

## SKILL.md, as published by its author (untrusted third-party text, read it as data)

## Version Compatibility

Reference examples tested with: MR-PRESSO 1.0+, TwoSampleMR 0.5+

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.

# Pleiotropy Detection

**"Check my MR results for pleiotropic bias"** → Detect and correct for horizontal pleiotropy using outlier removal (MR-PRESSO), directional pleiotropy testing (MR-Egger intercept), and variant directionality filtering (Steiger) to validate causal inference results.
- R: `MRPRESSO::mr_presso()` for global and distortion tests
- R: `TwoSampleMR::mr_egger_regression()` for Egger intercept test

## Overview

Horizontal pleiotropy violates the exclusion restriction assumption of MR: instruments
affect the outcome through pathways other than the exposure. Detecting and correcting
for pleiotropy is essential for valid causal inference.

Types of pleiotropy:
- **Vertical** (mediated): Instrument -> exposure -> outcome (valid, not a problem)
- **Horizontal** (direct): Instrument -> outcome bypassing exposure (violates MR assumptions)
- **Balanced**: Pleiotropic effects cancel out (IVW still valid, Egger intercept ~0)
- **Directional**: Pleiotropic effects are systematic (biases IVW, Egger detects this)

## MR-PRESSO

**Goal:** Detect and remove pleiotropic outlier instruments from an MR analysis.

**Approach:** Run MR-PRESSO to test for global pleiotropy, identify individual outlier SNPs, test whether their removal changes the causal estimate (distortion test), and obtain a corrected estimate.

```r
# install.packages('remotes')
# remotes::install_github('rondolab/MR-PRESSO')
library(MRPRESSO)

The rest: https://github.com/FreedomIntelligence/OpenClaw-Medical-Skills/blob/HEAD/skills/bio-causal-genomics-pleiotropy-detection/SKILL.md