Genotype imputation in admixed populations has not performed as well, because their genetic diversity is greater than the original reference populations [6]. In African Americans, combining YRI with at least one other reference population boosts imputation performance when compared to YRI alone [5], [7], [8], but an optimal imputation strategy is not well established. Two or more reference populations can be combined in their entirety [9], [10], combined in equal proportions [11], [12], or weighted to match the ancestral proportions of the study population [13], [14]. Alternatively, the imputation procedure can be conducted sequentially (once for each selected reference population) rather than as a combined population, followed by merging the imputed genotypes [15], [16]. Most recently, advancements in imputation software have been developed to create tailored reference panels for individual study subjects using all available reference populations as a starting point [17]. This type of approach is particularly attractive for admixed populations and is promoted for its simplistic and practical use for investigators.
