One of major unknowns for psychiatric disorders is the nature of the genetic models by which variation at the DNA level increases risk for the clinical phenotype. For Mendelian disorders, a genetic model can be hypothesized by examination of pedigrees (e.g., dominant, recessive, or sex-linked) and knowledge of prevalence. For psychiatric diseases, we assume complex inheritance (allowing for mixtures of genetic and environmental effects along with diagnostic imprecision). Two genetic models have received particular attention, that complex traits are caused by common versus rare genetic variation. In the former, psychiatric disease results from the cumulative effect of many genetic variants each of which is common in the population and which confer subtle genetic risk (common disease/common variant model, CDCV). In the latter, psychiatric disease results from many different mutations each of which is rare but of powerful effects (multiple rare variant model, MRV).
