The comparison of case to control CNVs allows for the possibility of nonrandom CNV location unrelated to disease (i.e., CNVs tend to occur in specific locations of the genome, and this is unrelated to case status). A one-sided test for an excess of genes affected by case CNVs was performed. The inclusion of CNV size in the regression allows for case CNVs being of different size than typical CNVs (and thus likely to affect more genes, regardless of function). Inclusion of the total number of genes affected outside the gene set in the regression corrects for case CNVs affecting more genes overall (regardless of function) than control CNVs. Analysis was restricted to gene sets containing at least eight gene hits in total (case and control combined), since pathways with a large number of gene hits are more likely to be biologically meaningful. This criterion is different from that used for the ALIGATOR analysis of GWAS data (two significant genes) for two reasons. First, each gene is counted only once in ALIGATOR but can be counted multiple times in the CNV
