Our Review indicates two pathways forward. First, there is no reason to suppose that undifferentiated MD is intractable to GWAS, but success will require very large sample sizes (Figure 3). However, interpreting the results of such a study is likely to be challenging. We have seen that MD is highly comorbid with anxiety, and etiologically heterogeneous, at both genetic and environmental levels. Without information on comorbidity, known risk factors, and clinical phenotypes, the role of each locus will be unclear. Some will be sex specific, some will act only in situations of environmental stress, and others will predispose to anxiety. Genetic studies will need to include an extensive amount of phenotypic information if we are to make sense of hard-won mapping results.
