We focused on rare inherited variants matching the following criteria: size spanning ⩾10 consecutive SNPs for deletions and ⩾20 SNPs for duplications, and present in at least one parent along with one or more related probands but not in the healthy control set. A total of 222 CNVs (158 deletions and 64 duplications) from 154 probands met these criteria (Supplementary Table S1). The median variant size was 102 kb (range from 7.75 to 1775 kb) with 116 of the CNVs (52%) overlapping one or more genes. The CNVs encompassed or overlapped 229 distinct genes, 23 of which were associated with CNVs from multiple individuals. The largest family of genes affected was the olfactory receptor superfamily (54 genes, including 35 genes associated with a single duplication). Numerous recent studies have shown that olfactory receptors are rapidly evolving, mainly because of an unusually high rate of structural variation and close association of many family members with segmental duplications.30, 31, 32 As these genes are overrepresented in our CNV set and present a skewed distribution that might bias our ability to detect pathway enrichment, these genes were removed from subsequent analyses. This reduced our ADHD CNV gene set to 175 genes.
