A single nucleotide polymorphism in the ghrelin receptor gene (GHSR) was significantly associated with higher alcohol use scores and smoking in over 4,000 Finnish adults, supporting the role of ghrelin peptide signaling in addiction.
P = 0.0002Association between the GHSR gene variant rs2948694 and smoking in a dominant genetic model across 4,161 participants
What the researchers found
The minor allele of the rs2948694 SNP in the ghrelin receptor gene (GHSR) was associated with higher AUDIT scores (P = 0.0204, recessive model) and smoking (P = 0.0002, dominant model) in 4,161 Finnish adults. Post hoc analysis showed this risk allele was also associated with increased likelihood of high-level alcohol problems (AUDIT scores ≥ 16; P = 0.0043, recessive model).
Two SNPs in the pre-proghrelin gene (GHRL) — rs4684677 (Gln90Leu) and rs696217 (Leu72Met) — were not significantly associated with alcohol use or smoking outcomes.
Why it matters
Addiction has a strong hereditary component, and understanding which genes contribute to risk can help identify new therapeutic targets. Ghrelin is a peptide already known to influence reward and motivation in animal models. This study provides human genetic evidence supporting the same connection, suggesting that drugs targeting the ghrelin receptor — some of which are already in development — could potentially be repurposed for treating alcohol and nicotine addiction.
How the study worked
Researchers genotyped three single nucleotide polymorphisms (SNPs) — two in the ghrelin gene (GHRL) and one in the ghrelin receptor gene (GHSR) — in 4,161 individuals from a Finnish population-based cohort (the Genetics of Sexuality and Aggression project). Alcohol use was measured using the AUDIT (Alcohol Use Disorders Identification Test) questionnaire. Associations with AUDIT scores were tested using linear regression, and associations with smoking were tested using logistic regression.
What this study cannot tell us
This is an observational genetic association study and cannot prove that the GHSR variant causes higher alcohol use or smoking. The association with AUDIT scores was nominally significant (P = 0.0204), which may not survive correction for multiple comparisons. The cohort was entirely Finnish, limiting generalizability to other populations. AUDIT is a self-report questionnaire, which may underestimate actual alcohol consumption. Replication in independent cohorts is needed.
How to read the evidence
This is a population-based genetic association study with a substantial sample size (n=4,161). However, the findings are nominally significant and require replication. Genetic association does not establish causation, and the study is cross-sectional.
When this study was published
Published in 2016, this study remains relevant as ghrelin receptor antagonists continue to be explored for addiction and metabolic applications. The genetic associations identified here are still part of the active research landscape.
The bigger picture
This study adds human genetic evidence to a growing body of preclinical research showing that ghrelin signaling drives reward-seeking behavior. While ghrelin was originally studied for its role in appetite and growth hormone release, its involvement in addiction represents an expanding frontier in peptide biology. If the ghrelin receptor pathway is confirmed as a meaningful contributor to addiction risk, existing ghrelin receptor antagonists could potentially be evaluated as addiction therapeutics.
Questions still open
- Would ghrelin receptor antagonists reduce alcohol consumption or smoking cessation difficulty in humans carrying this risk allele?
- Does the rs2948694 variant alter ghrelin receptor expression or function, and through what mechanism does it influence addiction risk?
- Do these genetic associations replicate in non-Finnish populations with different drinking cultures?
Common questions
What is ghrelin and why might it be linked to addiction?
Does having this gene variant mean you'll become addicted to alcohol or nicotine?
Read the original research
Genetic variation of the growth hormone secretagogue receptor gene is associated with alcohol use disorders identification test scores and smoking.
Addiction biology, 21(2), 481-8
Citation
Suchankova, Petra; Nilsson, Staffan; von der Pahlen, Bettina; Santtila, Pekka; Sandnabba, Kenneth; Johansson, Ada; Jern, Patrick; Engel, Jörgen A; Jerlhag, Elisabet. (2016). Genetic variation of the growth hormone secretagogue receptor gene is associated with alcohol use disorders identification test scores and smoking.. Addiction biology, 21(2), 481-8. https://doi.org/10.1111/adb.12277