Table 1.
Considerations for Phenotype Selection in Phenomics Research
| Genetic Validity |
| a) moderately high heritability; association with related disorders in family members |
| b) relate to known common functional genetic variation |
| Measurement Properties |
| a) reliability (nomothetic validity, internal consistency); test-retest reliability (at least within a particular state, and preferably across states in illnesses which have an episodic pattern); and other desirable psychometric properties (e.g., discriminating power across a broad range of individual differences) |
| b) have good concurrent validity (convergent and divergent validity) with respect to hypothesized endophenotypes |
| Relevance for Human Applications |
| a) related to higher level constructs in humans, enabling links to clinical effectiveness and outcomes |
| b) suitable for application in clinical trials |
| c) associated with neuropsychiatric morbidity |
| d) cross-disorders relevance – the phenotype construct has been identified as important in more than one diagnostic syndrome |
| Relevance for Translational Investigation |
| a) homologies of expression across species enabling both basic and clinical investigation |
| b) latent endophenotype constructs relate to neural systems models sufficiently well studied that physiologically plausible manipulations can be effected and measured using currently available techniques |
| c) implicated neural systems already are targets of known partially effective treatments for existing disorders, or these systems are the targets of new chemical entities |
| Knowledge of Environmental Effects |
| a) known environmental effects on phenotype expression can usefully constrain modeling of phenotypic variance explained by genotypic variance, and may be particularly valuable in model organisms where environments can be strictly controlled (epigenetic mechanisms are seen as an area of rapid expansion in knowledge and systems in which these can be studied effectively may be prioritized |