Imputation methods work by combining a reference panel of individuals genotyped at a dense set of polymorphic sites (usually single-nucleotide polymorphisms, or “SNPs”) with a study sample collected from a genetically similar population and genotyped at a subset of these sites. Figure 1 shows a schematic example of such a dataset. Imputation methods predict unobserved genotypes in the study sample by using a population genetic model to extrapolate allelic correlations measured in the reference panel. The imputed genotypes expand the set of SNPs that can be tested for association, and this more comprehensive view of the genetic variation in a study can enhance true association signals and facilitate meta-analysis [9],[10].
