EtienneNtumba/PRSet-Tanzania
Domaine:
healthcareCréateur:
Eti
Hôte:
PRSet pathway-based PRS analysis and reports for the Tanzania sickle cell cohort.
# PRSet Pathway Analysis: Fetal Hemoglobin in Tanzanian Sickle Cell Disease
---
## 📊 Overview
This repository contains a comprehensive **pathway-based polygenic risk score (PRS) analysis** of fetal hemoglobin (HbF) levels in Tanzanian sickle cell disease (SCD) patients using **PRSet** (Polygenic Risk Score - competitive gene Set Test) implemented in PRSice-2.
### Study Highlights
- 🧬 **1,944 biological pathways** tested across 4 complementary databases
- 👥 **1,527 individuals** from Tanzania (held-out validation cohort)
- 📈 **8.4 million SNPs** from GWAS summary statistics
- 🔬 **Competitive permutation testing** (1,000-5,000 permutations)
- 🌍 **African population** - addressing underrepresentation in genetic research
- 📝 **Transparent reporting** - including negative results
### Key Finding
**No statistically significant pathway enrichment detected** after rigorous competitive permutation testing. This important **negative result** suggests that HbF genetic architecture in this cohort is **oligogenic** (dominated by few major loci like BCL11A) rather than **polygenic** (distributed across many pathways).
---
## 📑 Table of Contents
- Background
- Study Design
- Pathway Databases
- Methods
- Results Summary
- Repository Structure
- Requirements
- Installation
- Usage
- Interpretation
- Citation
- Team
- License
---
## Background
### Why Pathway Analysis?
Genome-wide association studies (GWAS) identify individual genetic variants, but **pathway-based analyses** offer complementary insights by:
1. **Aggregating weak signals** across functionally related genes
2. **Improving statistical power** for distributed polygenic effects
3. **Providing biological interpretation** through pathway enrichment
4. **Revealing mechanisms** not apparent from single-variant analysis
### Fetal Hemoglobin in Sickle Cell Disease
**Fetal hemoglobin (HbF)** is the most important genetic modifier of SCD severity:
- **Higher HbF** → Reduced sickling, fewer complications, be …