The enrichment test performed within the DAVID software does not correct for certain biases of CNVs toward certain functional classes of genes and large genes in particular. In order to correct for these biases we applied two permutation-based tests to the pathways found to be enriched by DAVID. First, we performed a case-only permutation-based test by constructing empirical null distributions that took the CNV size distribution and gene number into account. We randomly placed 10,000 sets of CNVs (same number of events, size distribution) throughout the genome. Placement on any autosome was allowed, but we sampled such that placement on chromosomes was weighted in proportion to the total number of de novo CNVs observed on the respective chromosome. We controlled for the number of genes impacted by CNVs by discarding individual permutations that intersected with more or less than the number of genes impacted in the observed data (± 10 genes). This procedure led to 1,000–2,000 permutations of null hypothesis CNV sets each for the bipolar, schizophrenia, and control de novo CNV sets. Significance for each of the query pathways
