Although we agree that examining evidence for association at imputed markers can be extremely useful in the context of fine-mapping association signals, it is important to note that genotype imputation is also expected to increase the power of genomewide association studies. For example, Willer et al. (111) and Kathiresan et al. (43) showed that rs6511720, a common variant in the low density lipoprotein receptor gene (LDLR), was strongly associated with blood low density lipoprotein (LDL) cholesterol levels (Figure 3). The association signal was missed in an initial analysis that considered only genotyped SNPs because rs6511720 is not included in the Affymetrix arrays used to scan the genome in the majority of their samples and is only poorly tagged by individual SNPs on the chip (the best single marker tag is rs12052058 with pairwise r2 of only 0.21). Another example we have encountered concerns the genomewide association analysis of G6PD activity levels in a sample of Sardinian individuals (77, 94). There, analysis of directly genotyped SNPs revealed two sets of SNPs strongly associated (p < 5×10−8) with G6PD activity levels, one
