Several GWAS studies of human smokers have identified SNPs associated with risk of nicotine dependence (Bierut et al., 2008; Saccone et al., 2009) or cigarette consumption (Caporaso et al., 2009; Consortium et al., 2010). Bierut et al (2008) found a significant SNP (rs16969968, p=0.007) in the cholinergic nicotinic receptor α5 subunit, changing Aspartate (Asp) (major allele) to Asparagine (Asn) (minor allele) at position 398 (Bierut et al., 2008). Genotyping in African American (AA) and European-American (EA) participants revealed differential associations between populations, but the SNP was most significantly associated with nicotine dependence in the combined samples (Bierut et al., 2008). Recently, Oni and colleagues examined hiPSC-derived neurons from patients with and without the CHRNA5 Asn-398 allele (Oni et al., 2016). Patient somatic cells from the Collaborative Genetic Study of Nicotine Dependence (COGEND) were reprogrammed into hiPSC and differentiated into primarily dopaminergic neurons, with about 20% glutamatergic neurons. Neurons containing the Asn-398 allele exhibited an increase in the amplitude and frequency of spontaneous excitatory post synaptic currents, compared to Asp-398 neurons (Oni et al., 2016). Glutamatergic neurons, but not DA neurons,
