Using EEG power as an endophenotype, the COGA project reported genetic linkage and linkage disequilibrium between beta and a GABAA receptor gene (Porjesz et al., 2002a). Beta rhythm is generated in a network of excitatory pyramidal cells and inhibitory interneurons involving GABAA action as the pacemaker (Whittington et al., 2000). The same GABAA receptor gene (GABRA2) associated with beta EEG was also associated with alcohol dependence (Edenberg et al., 2004), a finding that has been replicated (Covault et al., 2004) and expanded to include other substance dependence in adults and conduct disorder in adolescents (Agrawal et al., 2006; Dick et al., 2006). The involvement of the GABAergic system in AUDs is supported by neuroimaging studies, which indicate deficient GABA benzodiazepine receptors in the brains of alcoholics (Abi-Dargham et al., 1998; Lingford-Hughes et al., 1998) and HR offspring (Volkow et al., 1995). Dysfunction in GABAA receptor genes may affect neural excitability, or the imbalance between excitation-inhibition (hyperexcitability) reflected in increased beta observed in alcoholics and HR offspring; this in turn may be involved in the predisposition to develop AUDs and related disinhibitory disorders.
