Three of these studies used pooled DNA samples (Mah et al., 2006; Shifman et al., 2008; Kirov et al., 2009b). This cost-effective method is effective in identifying disease genes (e.g. Liu et al., 2005; Johnson et al., 2006), although it is less sensitive than individual genotyping due to measurement errors in DNA quantification and results in reduced power. A further limitation of this method is that the evaluation of data is limited to the study of (estimated) allele frequencies at the level of individual SNPs. It cannot detect effects of haplotypes, interaction between SNPs, and effects of genotypes that do not show up in allele frequency differences. The best supported variants in these studies did not achieve genome-wide significance (Mah et al., 2006; Shifman et al., 2008; Kirov et al., 2009b) (see Table 1).
