The intuitive appeal of the signal coming from CHRNA3/CHRNA5 arises from the putative effects of rs16969968 on receptor function (but not expression). As α4β2α5 receptors with the asparagine residue show decreased response to a nicotine agonist, carriers may require greater amounts of nicotine and thus, be more vulnerable to dependence [47] (but see also [54]). In addition, α5 knock-out mice appear to be more sensitive to the rewarding effects of nicotine, particularly at higher concentrations, demonstrating profound increases in motivation to seek and consume nicotine [55].
