This study provides the first evidence for association between the CHRNB3/A6 genes and alcohol behaviors in humans. In CHRNA6, SNP rs892413 (p=0.0033) reached statistical significance using a conservative threshold, as did SNP rs13280604 (p=0.0053) in CHRNB3. Two other SNPs in CHRNA6 (rs1072003 and rs2304297) were nominally significant. Our findings, coupled with the recent evidence for polymorphisms in these receptors contributing to susceptibility to nicotine dependence (Bierut et al., 2007; Hoft et al., 2008; Saccone et al., 2008; Saccone et al., 2007) supports the hypothesis that nAChR genes may contribute to the co-morbidity of smoking and alcohol problems. This is consistent with results from in vitro systems and animal work showing that alcohol modulates the binding of nicotine to nAChRs (Aistrup et al., 1999; Dohrman & Reiter, 2003; Jerlhag et al., 2006).
