In imputation studies, the reduced portability of tag SNPs previously observed in populations genetically intermediate among reference groups and in African populations has taken the form of reduced imputation accuracy for these populations68, and consequently, reduced statistical power for imputation-based association mapping69. The accuracy of imputation depends largely on the same two factors that influence portability in the tag-SNP case. First, the overall level of LD in a study population reflects the distance over which the genotypic correlations that permit imputation extend, so that imputation is more accurate in high-LD populations68. Second, imputation accuracy is influenced by the level of genetic relationship of the study population to the reference population8,68, which affects the utility of the haplotypes copied from the reference population in imputing genotypes in the study population. In an assessment of imputation accuracy in 29 populations worldwide, similarly to the tag-SNP case, imputation accuracy based on HapMap reference panels was highest in European populations closely related to the HapMap CEU panel, and lowest in African populations and populations genetically intermediate between the panels68 (Fig. 4). Use of mixture
