MACH (Li, Willer, Ding, Scheet, & Abecasis, 2010) on data that are pre-phased using SHAPEIT (Delaneau, Zagury, & Marchini, 2013). Pre-phasing refers to the computational process of constructing haplotypes, or linear combinations of alleles along a chromosome, prior to imputation. The primary advantage of pre-phasing is a dramatic improvement in the speed of imputation. The 1000 Genomes Project sample is commonly used as a reference (1000 Genomes Project Consortium et al., 2010). In samples where diverse genetic backgrounds are present, it is common to use multiple or all reference samples within the 1000 Genomes Project. Importantly, each approach to imputation generates a measure of imputation confidence which can be used in subsequent tests to account for uncertainty. A typical approach is to recode the genotype to capture uncertainty. For example, two alleles imputed with 99% certainty would be coded as .99 and summed to create a genotype 1.98, representing two nearly certain alleles comprising a homozygous genotype.
