Parameter estimates for the reference panel can be precalculated and saved to speed up the imputation process. To examine the importance of GWAS panel individuals during the parameter estimation step, we used 938 unrelated individuals from 53 worldwide populations from the Human Genome Diversity Panel36. We compared the imputation accuracy across three parameter estimation methods: constant parameters (θ = 0.001 and ε = 0.01), reference panel only for updating the parameters using a leave-one-out method, and reference and GWAS panels for updating. The results of imputation accuracy evaluated on ~6,000 masked variants from chromosomes 20–22 on the ExomeArray are shown in Supplementary Figure 3. We see that updating the parameters results in increased imputation accuracy in comparison to constant estimates (especially for European samples, where imputation r2 increases from 0.35 to 0.45 in the lowest MAF bin). However, including the target panel (along with the reference panel) typically produced only a very small improvement in imputation accuracy.
