One testable hypothesis is that GWAS would be more powerful and efficient if we select imaging phenotypes in a principled way; if this is true, it may be possible to perform GWAS with consistently replicated hits, that do not require tens of thousands of subjects to reject the null hypothesis. In fact, the ENIGMA working groups each aim to find heritable brain measures that maximize case–control differentiation, for studies of disease. This will help us to prioritize the future targets of study for influential genes. Although ENIGMA is data-driven, that does not mean that we cannot use patterns in the findings to design more targeted approaches that prioritize phenotypes and genetic loci for follow-up analyses.
