Our results highlight the importance of rare CNVs for simplex ASD. We confirm an over-representation of rare de novo events in probands versus siblings with an odds ratio of 3.55 for all variants and 4.02 for rare de novo genic variants. Using a novel approach to assessing significance specifically for recurrent de novo CNVs, we find very strong evidence for the contribution of duplications at 7q11.23, showing, for the first time., genome-wide association in a case-control study. Moreover, we identify four additional rare recurrent de novo events restricted to probands. Two of these, 16p13.2 and the CDH13 locus, are novel ASD loci and two, 1q21, 15q13.2-13.3, have been previously implicated in neuro-developmental disorders including ASD. Each of these four regions also show rare transmitted CNVs exclusive to probands. Finally, we find compelling evidence confirming the association of both 16p11.2 duplications and deletions.
