“…rs16969968 encodes an amino-acid substitution in CHRNA5 that might mediate some of these risk effects, and several lines of evidence support this hypothesis. A proposed risk mechanism, based largely on animal models, suggests that the CHRNA5 risk allele increases the heaviness of smoking by attenuating the aversive response to nicotine (Bailey et al, 2010;Bierut et al, 2008;Fowler et al, 2011;Fowler et al, 2013;Frahm et al, 2011;Jackson et al, 2010;Kuryatov et al, 2011;Saccone et al, 2010;Saccone et al, 2007;Tobacco and Genetics Consortium, 2010). However, this mechanism has not been directly examined in human studies.…”