We then expanded our analysis to include candidate associations with nominal significance, as the above analysis is likely to be overly conservative due to the high level of dependence between neighboring genes. An IPA of genes with a nominal p < 0.02 identified the same functional categories as above suggesting that a large proportion of the nominally significant genes are likely relevant to morbidity. In addition to identifying genes within known genomic disorders, this analysis identified genes outside of these intervals. For example, we observed an excess of smaller deletions of SCN1A specifically in patients with epilepsy (p = 0.019), consistent with the literature27. CD44 deletions on 11p13 are significant in craniofacial cases (p = 0.010) and have previously been linked to cleft lip and palate in SNP and expression microarray studies28,29. A region on 9p24 containing five genes is significant in craniofacial cases, with the peak significance focused at SLC1A1 (peak p = 0.00172), a high affinity glutamate transporter previously implicated in multiple neurological conditions30. This peak, specific to SLC1A1, is also significant in neurological, craniofacial and epilepsy cases.
