Importantly, it is still not clear how CHRM2 is involved in externalizing behavior at the functional level. Multiple SNPs were selected for genotyping in this sample, based on prior evidence of association with externalizing psychopathologies in the COGA sample (Dick et al., 2008; Wang et al., 2004). However, none of these SNPs has known functional properties; none are directly involved in altering the protein product of the gene. Rather, it is assumed that these SNPs are correlated with the (unknown) functional variant(s), which would also contribute to different degrees of significance detected with different SNPs (as found in this study and previous ones). Because there are multiple locations across genes where variation could contribute to differences in gene function or regulation, testing multiple SNPs across a gene is considered the optimal strategy for candidate gene studies (“Biological Psychiatry,” 2009). The fact that the associated SNPs (across this study and previous ones) span different regions of the gene also suggests that there may be multiple variants in the gene that have functional effects that contribute to differential susceptibility to externalizing behavior.
