For common SNPs (MAF ≥5%), the larger HapMap 3 reference panel made only a slight difference to the already excellent performance (mean r2 increased from 0.946 to 0.961). However, as expected there was greater improvement for rare (MAF <0.5%) and low-frequency SNPs (MAF = 0.5–5%). Their combined mean r2 increased from 0.60 to 0.76, driven by a large subset of rare SNPs (41%) and low-frequency SNPs (25%) where r2 increased by at least 0.1, yielding mean r2 improvement for these subsets of 0.62 and 0.49 respectively (Fig. 5a, b and Supplementary Table 8). This improvement occurred mainly at SNPs with unobserved minor alleles in the HMII-CEU reference panel that became informative in the larger CEU+TSI panel (see Supplementary Tables 9 and 10 for the effect of reference panel size on imputation accuracy in other populations).
