Classic studies heralded the importance of CNVs in neuropsychiatric disorders.54–58 Explosive progress in this area resulted from microarray methods that permitted genome-wide discovery of CNVs in large population samples.59–61 While evidence for association of large, highly recurrent CNVs with disease represents among the strongest findings in psychiatric genetics, this result has to contend with two challenges: 1) each CNV generally contains numerous genes; and 2) there is a high degree of loci sharing across disorders. The present study seeks to address these challenges through a novel and highly systematic approach to establishing the distribution of CNVs (deletions and duplications separately) as susceptibility factors across common disorders of cognitive development. The most prominent finding of our study was the high extent to which all disorders are subsumed by ID. Even under strict criteria, 96% of all genes identified by CNVs were associated with ID and greater than 90% of genes for the other disorders were also found in ID. In addition to this contribution, our study has elucidated mechanisms that are enriched in a given disorder or may be shared by disorders.
