We expect that the best use of intermediate phenotypes will not lie in aiding gene identification but in interpreting the results of GWAS of psychiatric disease, through a variety of existing and novel study designs (see Box 3). The heterogeneous origins of many psychiatric disease, and the recognition that they may have little biological coherence (at a genetic level), suggests that genetic mapping alone may not be particularly useful for revealing how disease arises [59]. Having a phenotype that reflects a real, or even hypothesized, mechanism of how a gene acts on disease will be extremely useful. To take one example, there is considerable evidence that major depression is comorbid with anxiety disorders [68–77]. If we map depression and anxiety in the same subjects, we will be able to distinguish genetic loci that contribute specifically to one or the other disorder, and also find loci that affect both [78, 79]. This information is required for understanding the pathway by which genetic risk for depression results in disease. The expanding literature on examining the association between intermediate phenotypes and markers found
