EtienneNtumba/-GWAS-of-Sickle-Cell-Disease-in-Tanzania-Using-Regenie

# **Genome-Wide Association Study (GWAS) of Sickle Cell Disease in Tanzania Using Regenie** ## **1. Introduction** Genome-wide association studies (GWAS) are used to identify genetic variants associated with complex traits and diseases. This study focuses on **Sickle Cell Disease (SCD) in Tanzania**, aiming to detect **genetic variants significantly associated with the phenotype of interest** using **Regenie**, a two-step approach suitable for large-scale GWAS. **Key Details:** - **Total Samples:** 3,210 individuals. - **Original SNPs:** 8,457,145 (before quality control). - **Post-QC SNPs:** 1,466,733 (after applying quality control). - **Phenotype Type:** Continuous variable. - **Software Used:** `PLINK` for quality control, `Regenie` for association testing. - **Analysis Type:** GWAS with **stepwise regression modeling in Regenie**. --- ## **2. Quality Control (QC) Using PLINK** Before conducting a GWAS, it is **crucial to perform QC** to ensure **reliable** and **valid** results by removing: - **Low-quality SNPs** (e.g., missing data, low minor allele frequency). - **Samples with excess heterozygosity** (potential genotyping errors). - **Population structure issues** (through pruning of correlated SNPs). ### **Step 1: SNP and Sample Filtering** We apply the following **PLINK filters**: ```bash plink --bfile "$BFILE" \ --geno 0.02 \ # Remove SNPs with >2% missing genotypes --mind 0.02 \ # Remove individuals with >2% missing genotypes --maf 0.01 \ # Exclude SNPs with Minor Allele Frequency (MAF) 0.05 || $6 "$OUTDIR/remove_het_samples.txt" plink --bfile "$OUTDIR/step2_ld_pruned" \ --remove "$OUTDIR/remove_het_samples.txt" \ --make-bed --out "$OUTDIR/QC_passed" ``` **Why?** - Samples with **excess heterozygosity (|F coefficient| > 0.05)** may be **misgenotyped or contaminated**. --- ## **3. GWAS Analysis Using Regenie** ### **Why Regenie?** - Efficient for **large-scale genetic data**. - Uses **stepwise ridge regression**, reducing confounding by p …