Recently there has been considerable interest in the imputation of missing genotype data for the analysis of genome-wide association (GWA) studies. The availability of panels of extensively genotyped reference samples, such as those from The International HapMap Project [HapMap; International HapMap Consortium, 2007] and now the 1,000 Genomes Project, has allowed for the indirect measurement of SNP genotypes that were not directly typed in a genetic association study but typed in the reference samples. This strategy has aided the discovery of multiple loci associated with disease [e.g. Barrett et al., 2008; Scott et al., 2007; The Wellcome Trust Case Control Consortium, 2007] or quantitative traits [Lettre et al., 2008; Loos et al., 2008; Willer et al., 2008]. For example, in Willer et al. [2008], the LDLR (cholesterol receptor) signal was detected only after imputation was performed, since the associated variant (rs6511720) was poorly tagged in samples genotypes with the Afymetrix 500K array set (maximum R2≈0.21).
