studies have been mixed in terms of CNV burden.69–71 McCarthy et al.16 conducted a meta-analysis and found 16p11.2 (specifically duplications) highly enriched in bipolar disorder, which has also been identified in ID, ASD, schizophrenia, and epilepsy. However, additional studies have not identified any significant specific CNVs.69, 71 Overall, our studies strongly suggest that, in general, there is a little evidence that single CNVs confer susceptibility to individual disorders. Instead it seems as if individual CNVs large confer susceptibility to a broad array of disorders. These results lead to the question: As CNVs confer susceptibility to neuropsychiatric disorders (a fact that is now unequivocal), how is disorder specificity established? Is it stochastic, dependent on interaction with other genetic and/or environmental factors? Indeed, one recent study has demonstrated that approximately 10% of people with ID and a single large CNV may have a second large CNV.72 This study suggests at least two possible hypotheses with regard to genetics. First, that disorder specificity may not be encoded in individual CNVs but in combination of CNVs; or alternatively, second, that disorder specificity may be coded in the overall burden measures with distinct thresholds for different disorders. Of course, these hypotheses will await deep genotyping
