East Asia, when imputation was applied to populations from the Middle East, Central and South Asia, the Americas or Oceania, it was generally better to use the combined HapMap sample as a reference than to use any single HapMap analysis panel as a reference. It is interesting to note that, in all cases, combining the three HapMap panels into a single reference set was either the best option or the second best option. Furthermore, in situations where this combined reference panel reduced imputation accuracy, it resulted in an average increase of only 0.15% in error rates. Our results are consistent with those of Huang et al. [Huang et al., 2009] who showed, in a smaller subset of HGDP populations and a different set of genotyped SNPs, that combined reference panels could outperform panels that included only one population. The figure also illustrates that, when a large number of individuals are genotyped in study samples, it may be possible to bypass the HapMap reference panel altogether. In the last panel, rather than using the HapMap genotypes to impute missing data, we used a combined dataset including all other HGDP populations.
