Although there is no clear consensus yet about the role of SNP imputation in the analysis of genome-wide association studies, high imputation accuracy can be achieved using model-based methods19-23 and can lead to an increase in power23,24. To illustrate the possibilities, in the 500-kb HapMap ENCODE region on 8q24.11 (Supplementary Fig. 5) we evaluated imputation of Phase II SNPs from the Affymetrix GeneChip 500K array. To do this, we used a leave-one-out procedure to assess the accuracy of genotype prediction in the YRI. For SNPs with MAF≥0.2, the average maximum r2 to a typed SNP in the region is 0.59 compared to an average genotype prediction r2 of 0.86. Furthermore, whereas 44% of such SNPs in the region have no single-marker proxy with r2≥0.5, fewer than 6% of the SNPs have a genotype imputation accuracy of r2<0.5, establishing that accurate imputation can be achieved even in the population where linkage disequilibrium is the weakest.
