The loss-of-function mutation (D398N) at the CHRNA5 gene rs16969968 locus increases nicotine addiction risk by reducing receptor calcium permeability, while VTA dopamine neurons in α5-knockout mice exhibit attenuated responsiveness to nicotine (Kuryatov et al., 2008; Morel et al., 2014; Sciaccaluga et al., 2015; Tapia et al., 2007). Here, CHRNA5 is linked to nicotine dependence.