In the case of BD, recent analysis of common genetic variation associated with BD susceptibility using powerful genome-wide approaches, has confirmed that BD is highly polygenic in nature with the suggestion that there may be many thousands of common variants that contribute small or modest levels of risk for BD6. Thus, for modeling of BD with iPSCs choosing individuals at random would make it difficult to identify individuals, affected or unaffected, that do not harbor risk alleles, especially common variants associated with the disease, and the selection of a genetically appropriate control is problematic. Moreover, randomly selected BD patients might also be expected to harbor variants that only modestly affect cellular phenotypes in cellular models. Alternatively, consideration of family history and the number of risk alleles an individual might harbor (i.e. the genetic load) when selecting individuals for reprogramming may allow one to select individuals from a pedigree enriched for BD in order to enrich for deleterious alleles. Following this rationale, the more psychiatric disease in the family the higher the genetic risk of any individual will be, and thus
