The second use of intermediate phenotypes is to interpret the results of genetic discovery studies. For instance, suppose, through a genomewide association study (GWAS) or exome sequencing, a number of genes are found that are unequivocally involved in conferring risk of schizophrenia. Either the function of these genes is completely unknown, or their role in psychiatric disease was never previously suspected. Genetic analysis of intermediate phenotypes might provide clues to the role these genes play. For instance, in the case of schizophrenia studies of high-risk individuals, together with birth and cohort studies, indicate that cognitive deficits predate the onset of psychosis [15, 16]. These cognitive features are heritable and are genetically correlated with psychosis (genetic correlations have been estimated to be greater than 0.5) [17–19]. Researchers might attempt to identify loci contributing to both variation in cognitive performance and risk of psychosis, and hence begin to unravel the function of one group of genetic risk factors for schizophrenia.
