In addition to electrophysiological findings, two studies examined associations between SNPs in the CHRM2 gene and alcohol dependence, drug dependence and affective disorders (Luo et al., 2005). Wang et al., (2004) studied 11 SNPs within the CHRM2 gene, relating them to four phenotypes (alcohol dependence, major depressive syndrome, either disorder or both) finding at least one significant finding for all SNPs. Interestingly, SNP rs1824024 showed significance across all phenotypes. This suggests that CHRM2 variation may be a risk factor for disorders typically characterized as externalizing such as alcohol dependence but also may be associated with more internalizing pathologies such as major depression. If so, the association of rs1824024 with P300 amplitude during childhood may suggest that those with the TT allele may be a greater risk for all types of psychopathology and not just substance use disorders. Future follow up and analysis of this question would be of interest in determining whether CHRM2 and P300 are specific predictors of SUD or, alternatively, reflect a common genetic/endophenotypic effect on future psychiatric outcome.
