Initial COGA studies using iPSC‐derived neurons focused on the CHRNA5 gene, encoding the α5 subunit of the nicotinic acetylcholine receptor, with variants that have been associated with dependence on nicotine, alcohol and other substances. Results showed that the minor allele of rs16969968, encoding a D398N amino acid replacement, produced neurons that were more sensitive to stimulation with lower concentrations of nicotine but were rapidly desensitized, predicting an altered effect on reward pathways. 37 Another functional coding variant associated with AUD is a non‐synonymous A118G (rs1799971; N40D) SNP in the OPRM1 gene, which encodes the mu opioid receptor (MOR) and has been also linked with an increased risk for drug addiction. 44 , 45 , 46 , 47 A118G is one of the most common SNPs in selected populations, affecting ~40% of Asian, ~16% of European and ~3% of African individuals. 48 This SNP encodes an amino acid substitution, replacing asparagine (N40) with aspartate (D40), thus removing a potential glycosylation site. Although the involvement of A118G in AUD has been controversial, 49 , 50 , 51 and there was no significant
