The third aim was addressed using SynGO24 (dataset version: 20210225) to test for enrichment among the 76 risk genes for genes involved in synaptic processes and locations. We analyzed for enrichment in two subsets: “biological process” (201 gene sets) and “cellular component” (92 gene sets). We controlled using a background set of “brain expressed” genes provided by the SynGo platform (defined as ‘expressed in any GTEx v7 brain tissues’) containing 18,035 unique genes, of which 1,225 overlap with SynGO annotated genes. For each ontology term, a one-sided Fisher exact test was performed to compare the list of ADHD risk genes and the selected background set. To find enriched terms within the entire SynGO ontology, the most specific term is selected where each ‘gene cluster’ (unique set of genes) is found and then multiple testing correction is applied using False Discovery Rate (FDR) on the subset of terms that contain these ‘gene clusters’. Only ontology terms with gene sets with a minimum of three genes were included in the enrichment analysis.
