Conduct problems, alcohol problems, and hyperactive–inattentive symptoms display moderate-to-high heritability in adolescence and co-occur at a high rate [1, 2]; this co-occurrence may be due in large part to shared genetic factors [1, 2]. Although identifying genes that contribute to this shared genetic influence is important, it is also important to identify mechanisms through which shared genes influence these phenotypes. The γ-aminobutyric acid (GABA) A receptor, α2 gene (GABRA2), located on chromosome 4, may play a role in externalizing phenotypes. From a biological perspective, there are several factors that might account for this association. GABA acts as the vertebrate brain's main inhibitory neurotransmitter [3], and GABAA receptors undergo allosteric modulation by drugs such as ethanol, benzodiazepines, and barbituates [4]. GABAergic interneurons within the ventral tegmental area are also primarily responsible for the inhibitory regulation of dopamine neurons [5, 6], which have long been implicated in impulsive and addictive behaviors [7].
