These lines of evidence suggest regulatory mechanisms by which the SNPs from this GWAS may affect the complex phenotype of ADHD. While individually each piece of evidence is relatively weak, they offer ways in which molecular biologists could proceed with further experiments that would more definitively establish mechanisms. For example, the GWAS-wide enrichment suggests global differential gene regulation in angular gyrus, which has been associated with hyperactivation in ADHD by fMRI (41) and suggests a tissue to study gene expression directly in animal models. ChIP-seq and motif data suggest specifically testing HNF4 binding differentially to the alleles of rs561543, and the strong motif coupled with eQTL data suggest looking at whether p300 binds differentially to rs864643 in a brain tissue model. Finally, MOBP eQTL evidence suggests experiments to dissect the mechanism of MOBP differential expression, perhaps modulated by p300 at rs864643 and suggests that it may be useful to perform ADHD-relevant behavioral assays of MOBP-deficient mice, which do not show an overt behavioral phenotype (42).
