The advantages of pre-phasing become particularly clear when considering successive reference panels that have been updated over time. Following a relatively modest pre-phasing investment, each new reference panel can be imputed at a low computational cost while improving the accuracy and completeness of the imputed genotypes. This point is illustrated by Table 2, which shows that adding haplotypes to the 1000 Genomes resource increased accuracy for all SNPs, especially those with minor allele frequency (MAF) of 1–3%: from a mean R2 of 0.65 to 0.75 to 0.82 in the WTCCC2; from a mean R2 of 0.69 to 0.73 to 0.83 in GAIN; and from a mean R2 of 0.49 to 0.55 to 0.61 in the WHI. Beyond the accuracy increase at known variants, each new panel also introduces many novel variants that could lead to additional association signals and biological insights.
