The galanin receptor 1 gene associates with tobacco craving in smokers seeking cessation treatment.

Craving for tobacco is a major challenge for people with nicotine dependence (ND) who try to quit smoking. Galanin (GAL) and its receptors (GALRs) can alter addiction-related behaviors and are therefore good candidates for modulators of behavioral parameters associated with smoking. We performed a genetic association study in 486 subjects (432 European American, EA) recruited for smoking cessation trials. Twenty-six candidate genes for ND-related phenotypes were selected based on the literature. Subjects were assessed using the Minnesota Withdrawal Scale (MWS), which included a specific item for craving, the Fagerström Scale of Nicotine Dependence (FTND), and other ND-related instruments. One single-nucleotide polymorphism (SNP) in GALR1, rs2717162, significantly associated with severity of craving in EA samples (p=6.48 × 10(-6)) and in the combined sample (p=9.23 × 10(-6)). Individuals with TT and TC genotypes had significantly higher craving scores than CC subjects. We also observed that SNPs in the CHRNA5 locus, rs16969968 and rs684513, which have been associated with ND-related phenotypes in previous studies, were nominally associated with FTND scores, although these results did not meet Bonferroni-adjusted criteria for experiment-wide significance. Our findings suggest that variation at GALR1 associates with differences in the severity of past craving for tobacco among smokers motivated to quit. Taken together with preclinical evidence, these results, if replicated, suggest that GAL and GALRs may be useful therapeutic targets for the pharmacological treatment of ND. Our results also confirm previously reported associations between variation at CHRNA5 and ND.