While it may not seem surprising that large de novo events carry the greatest risk for developmental disorders, it is interesting to note that we did not find evidence that ASD diagnosis or severity was mediated by intellectual disability (ID). It has been argued that ASD in the presence of ID may reflect an epiphenomenon, in which a non-specific impairment of brain functioning unmasks and/or exacerbates limitations in an individual's capacity for social reciprocity (Skuse, 2007). It has also been widely held that the detection of large de novo CNVs will be enhanced by the ascertainment of ASD samples with greater intellectual disability. Our data shows that large de novo CNVs confer substantial risk for ASD in the SSC, but they are only modestly correlated with lower IQ and largely independent of ASD severity.
