We next determined if our ADHD gene set was enriched for particular biological and disease processes. Using Ingenuity Pathway Analysis, the process categories neurological disease, psychological disorders, nervous system development and function and behavior were among the most significantly enriched categories in the ADHD gene set, even after application of a multiple test correction (MTC) (Table 4). Four of the six most highly enriched GO Biological Process categories were learning, cell adhesion, central nervous system development and hindbrain development (Supplementary Table S3), with learning and cell adhesion trending towards statistical significance after MTC application. When GO Biological Process analysis was restricted to genes that overlapped only CNV deletions, the classes representing learning and hindbrain development retained MTC-applied significance (Table 5). ADHD CNV genes associated with learning and cognition included ATM, CTNND2, GRM5, GRM7, PARK2, PTPRD and UNC13C. As an additional control to show the specificity and independence of the inclusion variables, the same CNV inclusion criteria and analysis strategies were reapplied using a large set of parent–child trios for congenital heart disease. The enriched pathway spectrum was almost entirely dissimilar in the cardiovascular cohort, and no neurological function classes were found significant, even without MTC application.
