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The multifaceted gut‐brain peptide ghrelin and its receptor ( GHSR ‐1a) are implicated in mechanisms regulating not only the energy balance but also the reward circuitry. In our pre‐clinical models, we have shown that ghrelin increases whereas  GHSR ‐1a antagonists decrease alcohol consumption and the motivation to consume alcohol in rodents. Moreover, ghrelin signaling is required for the rewarding properties of addictive drugs including alcohol and nicotine in rodents. Given the hereditary component underlying addictive behaviors and disorders, we sought to investigate whether single nucleotide polymorphisms ( SNP s) located in the pre‐proghrelin gene (  GHRL  ) and  GHSR ‐1a gene (  GHSR  ) are associated with alcohol use, measured by the alcohol use disorders identification test ( AUDIT ) and smoking. Two  SNPs  located in   GHRL  , rs4684677 ( G ln90 L eu) and rs696217 ( L eu72 M et), and one in   GHSR  , rs2948694, were genotyped in a subset ( n  = 4161) of a  F innish population‐based cohort, the  G enetics of  S exuality and  A ggression project. The effect of these  SNPs  on  AUDIT  scores and smoking was investigated using linear and logistic regressions, respectively. We found that the minor allele of the rs2948694  SNP  was nominally associated with higher  AUDIT  scores ( P  = 0.0204, recessive model) and smoking ( P  = 0.0002, dominant model). Furthermore,  post hoc  analyses showed that this risk allele was also associated with increased likelihood of having high level of alcohol problems as determined by  AUDIT  scores ≥ 16 ( P  = 0.0043, recessive model). These convergent findings lend further support for the hypothesized involvement of ghrelin signaling in addictive disorders.

Genetic variation of the growth hormone secretagogue receptor gene is associated with alcohol use disorders identification test scores and smoking