A contributing factor to the age specificity of the effect of the CHRM2 SNPs could be a frailty effect. The frailty effect would play a role if there were relatively easy access to alcohol in the youngest age range, at least for those most at risk. Among those who have the major alleles, those who are genetically most vulnerable become alcohol dependent rapidly, leaving only those who have some (unmeasured) protective factor(s). Thus risk for those with the major alleles will decrease with age, since those without the protective factors will have become alcohol dependent, leaving primarily those with protective factors at potential risk. We also note that if the illicit drug user population had easier access to alcohol than the entire population as a whole, the greater genetic effects seen in the illicit drug user subsample might in part be the result of a gene-environment interaction, akin to those described in Dick and Kendler (2012), in which looser social controls over behavior accentuate genetic effects. Since 80% of the illicit drug use subsample are from COGA rather than community
