There are limitations to a study like ENIGMA despite its strengths. The first is that many other types of genetic or epigenetic variation other than GWAS are important—rare variants, CNVs, expression and methylation analyses are all crucial; they simply have not yet been evaluated through ENIGMA, but that is likely to change in the future. In recent genome-wide complex trait analyses (“GCTA” analyses; Yang et al. 2011; Lee et al. 2011), Wray, Visscher and their colleagues have shown that GWAS data may account for a surprisingly high proportion of genetic variance in a trait, even when the individual predictive value of a given locus or SNP is low.
