EtienneNtumba/QC-GWAS-Tanzania

GWAS QC pipeline, reports and plots for the Tanzania cohort. # GWAS of Fetal Hemoglobin in Tanzanian Sickle Cell Disease Patients --- ## Overview This repository contains the complete genome-wide association study (GWAS) pipeline and results for investigating genetic determinants of fetal hemoglobin (HbF) levels in Tanzanian sickle cell disease (SCD) patients. The study employs rigorous quality control procedures and state-of-the-art mixed linear model association analysis (GCTA-MLMA) to identify genetic variants associated with this critical disease modifier. **Study Highlights:** - 📊 **8.4 million** SNPs analyzed - 👥 **1,683** individuals post-QC - 🧬 **Genome-wide significant** associations detected - 📈 **Excellent genomic control** (λGC = 0.987) - 🌍 **East African population** (underrepresented in GWAS) - 🏥 **Clinical relevance** for sickle cell disease management --- ## 📑 Table of Contents - Background - Study Design - Key Results - Repository Structure - Pipeline Overview - Requirements - Usage - Quality Control Metrics - Data Availability - Citation - Team - Acknowledgments - License --- ## Background ### Sickle Cell Disease and HbF Sickle cell disease (SCD) is a monogenic disorder caused by a mutation in the β-globin gene (HBB), resulting in production of abnormal hemoglobin S (HbS). SCD is most prevalent in sub-Saharan Africa, affecting millions of individuals. Clinical severity varies substantially among patients, with **fetal hemoglobin (HbF) levels** being the most important genetic modifier: - **Higher HbF** → Reduced disease severity - **Lower HbF** → More severe complications - **HbF heritability**: ~89% (highly genetic) ### Known HbF Genetic Loci Three major loci have been consistently associated with HbF levels: 1. **BCL11A** (chr2p16.1) - Most significant modifier 2. **HBS1L-MYB** intergenic region (chr6q23.3) 3. **HBB gene cluster** (chr11p15.4) - *cis*-regulatory variants ### Study Rationale African populations remain underrepresented in GWAS despite bearing the highest burden of SCD. …