Full details are provided in the Supplementary Material (Sections 1–3). All participants were genotyped with Affymetrix 6.0 arrays (Affymetrix) at the Broad Institute of Harvard and Massachusetts Institute of Technology. As an initial screen, we used Genotyping Console 4.0 software (Affymetrix, Santa Clara, CA, USA) to call autosomal CNVs, restricting initial calls to ⩾10 kb and ⩾10 probes. We next excluded individuals with >50 CNV calls, as these were outliers from the distribution, followed by CNV loci with a frequency >1% in the whole sample. We then excluded putative CNVs <15 kb, covered by <15 probes, or where >50% of their length overlapped low copy repeats. Calls compatible with a de novo were made if a proband CNV was not spanned >50% of its length by a CNV in either parent. Probands who had large numbers of apparent de novos (>10) were excluded. After this initial screen with relaxed criteria to capture as many potential de novos as possible, we measured probe Log2 ratios derived from PennCNV.27 We then used a slight modification of the MeZOD algorithm12 (Supplementary Section 3)
