Chunk #15 — Results — Analysis of rare de novo CNVs in the Simons Simplex Collection (SSC) — Rare, de novo, genic CNVs are over-represented in simplex probands
In fact, we found that de novo CNVs in probands were both larger and contained a greater number of genes when these measures were considered independently. We fit a series of stepwise linear models that increased in complexity from individual predictors to an analysis of covariance model, with size and affected status as predictors, to a three-term model that included the interaction of size and affected status. We confirmed a significant difference between probands and siblings with regard to the number of genes within CNVs (estimated β=11.1 more genes in a proband's de novo CNV; p=0.025) even after accounting for the strong effect of the size of the event (estimated β=6.8 genes per Mb; p=1.1 × 10−9) (Figure 3A). Considering deletions and duplications separately did not alter these findings. In summary, the burden of rare de novo CNVs is greater in probands with regard to number, size, and gene content.
