The contribution of rare CNVs (including both de novo and inherited variants) to ASDs is also apparent from case-control studies. A large-scale CNV study was undertaken by the Autism Genome Project (AGP) (Pinto et al., 2010). When comparing 996 ASD individuals of European ancestry to 1,287 matched controls, cases were found to carry a higher global burden of rare, genic copy number variants (CNVs) (1.19 fold, P = 0.012), especially so for genomic regions previously implicated in ASD and/or intellectual disability (1.69 fold, P = 3.4 × 10−4). These findings were independently replicated by Sanders et al (Sanders et al., 2011), when CNV burden analysis included both rare transmitted and de novo CNVs; however, a significant enrichment of CNVs was not observed exclusively among variants that were inherited (Levy et al., 2011; Sanders et al., 2011).
