Similarly, chromosome 7 was another region in COGA that had linkage to alcohol dependence diagnoses and electrophysiological endophenotypes (Jones et al., 2004; Wang et al., 2004). Just under the linkage peak was the gene CHRM2, which is an acetylcholine muscarin receptor. Muscarinic acetylcholine receptors activate a multitude of signaling pathways, and there is evidence they are involved in many brain functions, such as learning and memory, providing biological plausibility for its role in psychiatric and behavioral outcomes (Volpicelli & Levey, 2004). Like with GABRA2, genetic markers were tested across CHRM2, and alcohol-dependent individuals were found to be more likely to carry a particular version of the gene (Wang et al., 2004), a finding that was subsequently replicated in an independent sample (Luo et al., 2005). In the case of both genes, association was originally identified with adult alcohol dependence, but subsequent analyses demonstrated broader involvement in a number of externalizing disorders, including childhood conduct problems, adult antisocial behavior, and illicit substance use (Dick, 2007; Dick et al., 2008).
