While the use of matched sibling controls should preclude any confound of population stratification, we explored whether genotype data from the parents of probands with 16p11.2 or 7q11.23 CNVs suggested unusual ancestral clustering (Crossett et al., 2010; Lee et al., 2009) pointing to a particular haplotype that might increase the frequency of de novo events. We found no evidence for this. In addition, given the very large number of 16p11.2 CNVs in this study and the widespread attention afforded previous findings at this locus, we considered the possibility of ascertainment bias. A review of medical histories obtained at the time of recruitment revealed that parents had prior knowledge of a 16p11.2 CNV in 2 instances (1 de novo duplication, 1 transmitted deletion). Nonetheless, with these events removed, association of both deletions and duplications remains significant (p=3 × 10−19 all de novo events (N=10); p=2 × 10−14 deletions (N=7); p=0.002 duplications (N=3)) (Figure S4).
