Genome-wide significant loci on chromosomes 12 and 15 have more biological annotations supporting the co-localized genes. The credible set on chromosome 12 spans DUSP6, and includes an annotated missense variant in the first exon and an insertion near the transcription start site, though neither is the lead variant in the locus (Supplementary Data 4). DUSP6 encodes a dual specificity phosphatase71, and may play a role in regulating neurotransmitter homeostasis by affecting dopamine levels in the synapses72,73. Regulation of dopamine levels is likely to be relevant to ADHD since widely used ADHD medications have dopaminergic targets74,75 that increase the availability of synaptic dopamine. The chromosome 15 locus is located in SEMA6D, and the majority of variants in the credible set are strongly associated with expression of SEMA6D in fibroblasts76. SEMA6D is active in the brain during embryonic development, and may play a role in neuronal wiring77. Furthermore, variants in SEMA6D have previously been associated with eduational attainment78.
