We compared CNV content between the cases and controls excluding common CNVs (>1% population frequency). Consistent with previous studies of pediatric neurological disease3–5,17,18, we find a significant excess of large CNVs among cases relative to controls. This excess is evident at 250 kbp and becomes more pronounced with increasing CNV size (Figure 1A). For example, at a threshold of 400 kbp, ~25.7% (4,047 cases) of ID/DD children harbor an event of at least this size compared to 11.5% of controls, suggesting that an estimated 14.2% of ID and DD is due to the presence of CNVs >400 kbp in length (OR = 2.7, p = 5.86×10−158). At a threshold of 1.5 Mbp, we identify 1,782 (11.3%) affected individuals versus only 52 (0.6%) controls (OR = 20.3, p = 6.87×10−266) and at a threshold of 3.0 Mbp the odds ratio jumps to 47.7 (p = 1.68×10−197). There is a remarkably strong correlation (R2 = 0.97) with the de novo rate as a function of increasing CNV size, with 50% of events at 1 Mbp reported as inherited (Supplementary Figure 1).
