The second way in which biological coherence is important is when it refers to the ease with which genetic findings can be interpreted. For some complex diseases, genes identified through GWAS of the primary phenotype (i.e., disease susceptibility) have informed us about mechanism: inflammatory bowel disease [56], multiple sclerosis [57], and type 2 diabetes [58] provide examples. However, there is a legitimate concern that genetic mapping of psychiatric disease may provide little mechanistic insight because of the complexity of the phenotype [59]. Intermediate phenotypes are expected to suffer less from this problem, since they are not defined to meet the pragmatic demands of clinical utility, but rather supposedly correspond more closely to a biological substrate. An attraction of the biological coherence assumption is that intermediate phenotypes represent more biologically meaningful units than disease, and this will make genetic analysis easier.
