Genetic Epidemiology 36: 107–117 (2012) Genotype Imputation of Metabochip SNPs Using a Study-Specific Reference Panel of ∼4,000 Haplotypes in African Americans From the Women’s Health Initiative

Genetic imputation has become standard practice in modern genetic studies. However, several important issues have not been adequately addressed including the utility of study-specific reference, performance in admixed populations, and qual-ity for less common (minor allele frequency [MAF] 0.005–0.05) and rare (MAF < 0.005) variants. These issues only recently became addressable with genome-wide association studies (GWAS) follow-up studies using dense genotyping or sequenc-ing in large samples of non-European individuals. In this work, we constructed a study-specific reference panel of 3,924 haplotypes using African Americans in the Women’s Health Initiative (WHI) genotyped on both the Metabochip and the Affymetrix 6.0 GWAS platform. We used this reference panel to impute into 6,459 WHI SNP Health Association Resource (SHARe) study subjects with only GWAS genotypes. Our analysis confirmed the imputation quality metric Rsq (estimate