Rare CNVs in this locus (deletions and duplications) have previously been implicated in several psychiatric disorders (e.g., autism, schizophrenia, intellectual disability), as well as nonpsychiatric conditions, such as epilepsy (33), albeit with reduced penetrance. The duplicated region contains a plausible candidate gene for ADHD, CHRNA7 (Mendelian Inheritance in Man code *118511), which encodes the α7 subunit of the neuronal nicotinic acetylcholine receptor, a homo-oligomeric ion channel involved in calcium signaling in the brain. The α7 nicotinic acetylcholine receptor participates in an ADHD-relevant pathway by mediating dopamine release (34). Dopamine dysregulation is strongly implicated in ADHD; in fact, α7 receptor agonists show modest efficacy for the treatment of ADHD (35). Two candidate gene studies of microsatellite markers and a SNP in and near this gene in ADHD have been negative (36, 37). However, a recent study implicates the receptor in the response to stress and shows that maternal genotype has a strong effect on offspring phenotype (38). This might suggest that this gene is a particularly interesting candidate for parent-of-origin and gene-environment interaction studies in ADHD.
