Prior analyses of this [23] and other samples [20] found statistically significant and independent associations between nicotine dependence or heavy smoking and the four SNPs examined here or their high LD proxies. Of these SNPs only rs16969968 is known to be functional [23]. The minor allele at rs16969968 (A) results in an amino acid change (aspartic acid [D] to asparagine [N]) in the α5 neuronal nicotinic acetylcholine receptor subunit which reduces receptor function in vitro in response to a nicotinic agonist [19]. Finding a GxE interaction between this functional SNP and H.S. peer smoking is encouraging, suggesting that the interaction may be more than statistical and stand up to needed tests of replication in independent samples.
