The first few applications of genotype imputation on a genomewide scale also spent considerable effort in validating the accuracy of imputed genotypes. For example, in the first published account of the performance of genotype imputation in the context of a genomewide scan, Scott et al. (93) genotyped a set of type 2 diabetes cases and controls at approximately 300,000 SNPs. They then imputed genotypes at an additional >2 million SNPs to facilitate comparisons with the results of two other genomewide association scans for type 2 diabetes that relied on a different genotyping platforms (90, 117). To evaluate the accuracy of imputed genotypes, they contrasted imputed genotypes generated “in silico” with experimental genotypes generated in the lab for >500 SNPs, including 16 SNPs with imputation based p-values of <10−5 (see online supplementary material in ref. 93). Their results showed excellent concordance between genotype calls, estimated allele frequencies and test statistics for both types of data with an overall allelic discrepancy rate of <1.50% between genotyped and imputed SNPs.
