EROs have served as successful endophenotypes in the search for genes involved in alcohol dependence and related disorders in COGA. For example, in a large sample from densely alcoholism-affected families, the frontal θ ERO underlying P3 in experiments using a visual odd-ball paradigm exhibited significant genetic linkage to a DNA region on chromosome 7 (Jones et al. 2006b). Two excellent candidate genes—CHRM2 and GRM8—are located in this region, both of which encode components of neurotransmitter receptors. CHRM2 encodes an acetylcholine receptor—the M2 muscarinic receptor—whereas GRM8 encodes the metabotropic glutamate receptor 8 that belongs to a family of G-protein–coupled receptors (see figure 3). Significant associations were observed between the frontal θ EROs that were generated when COGA participants responded to a target stimulus and certain variants (i.e., single-nucleotide polymorphisms [SNPs]) in the CHRM2 gene. Similar associations were reported for δ EROs recorded from parietal-occipital brain regions (Jones et al. 2004, 2006a). These findings implicate CHRM2 in the generation and modulation of these oscillations underlying the P3 response to target stimuli. They are supported by the observations that the generation of θ
