The major neurochemical components contributing to θ and δ rhythms and P3 involve strong GABAergic, cholinergic, and glutamatergic system interactions (Frodl-Bauch et al. 1999). Accordingly, researchers also investigated the association of the second gene identified as a candidate in the COGA linkage analyses, the GRM8 gene, with θ EROs in response to target stimuli. GRM8 modulates glutamate-mediated signal transmission in the brain by inhibiting glutamate release at the synapse. The analysis revealed that θ EROs in the frontal, central, and parietal regions of the cortex were significantly associated with several SNPs in the GRM8 gene (Chen et al. 2008). Moreover, several of the same SNPs also were significantly associated with a diagnosis of alcohol dependence using ICD–10 diagnostic criteria.
