Absent definitive statistical evidence to support strong conclusions about the mechanism of the observed interaction between CHRM2 and parental monitoring, are there theoretical reasons to believe that CHRM2 could be involved in differential susceptibility? If CHRM2 were a plasticity gene, rather than a vulnerability gene, this could explain many puzzling features of the extant literature on CHRM2. We have focused here on the role of CHRM2 in substance use and externalizing outcomes; however, CHRM2 has also been associated with major depression in three independent samples (Comings et al., 2002; Luo et al., 2005; Wang et al., 2004) and with IQ in three independent samples (Comings et al., 2003; Dick, Aliev, et al., 2007; Gosso et al., 2006). In the studies that explicitly controlled for covarying conditions, it did not appear that the association across multiple outcomes (depression, alcohol dependence, IQ outcomes) was due to correlation among the phenotypes (Dick, Aliev, et al., 2007; Luo et al., 2005). However, these remarkably consistent early findings have more recently been joined by failures to replicate, with a new study finding no evidence of
