In considering how to properly address imperfect CGRs, it is important to note that having a small set of large studies, rather than a large set of small studies, does not necessarily abate the problem of imperfect genetic correlations. Despite the fact that having fewer studies can help to reduce the effects of heterogeneous phenotype measures, larger studies are more likely to sample individuals from different environments. If gene–environment interactions do play a role, strong differences in environment between subsets of individuals in a study can lead to imperfect genetic correlations within that study. The attenuation in power and accuracy resulting from such within-study heterogeneity may be harder to address than cross-study heterogeneity.
