What are the Genetic Influences of Alcohol Sensitivity and Alcohol Metabolism? A Narrative Review of Human Studies

Background: Alcohol sensitivity and alcohol metabolism are two phenotypes associated with alcohol use disorder (AUD) influenced by genetics. This narrative review aims to answer “What are the genetic influences of alcohol sensitivity and alcohol metabolism?” to gain a better understanding of the genetic aspects of AUD. Methods: A database search was performed in PubMed. Empirical human genetic studies published between 2009 and 2025 that focused on alcohol sensitivity (measured by the Self-Rating of the Effects of Alcohol scale) or alcohol-metabolizing genes were eligible for review. Studies were screened to determine inclusion for the current review. Findings: Fifteen studies were reviewed. Sample sizes ranged from 24 to 7,339 individuals. Study samples were largely of European ancestry, with fewer studies in individuals of African and Asian ancestries. Among the studies reviewed, a wide range of variants were shown to be associated with lower alcohol sensitivity, such as OPRM1 variants, while GAD1 variants and others were associated with higher alcohol sensitivity. Alcohol-metabolizing variants such as ALDH2*2 were shown to be protective against AUD, and others were associated with a greater risk of AUD, such as ALDH1A*1. Conclusion: An interesting variety of genetic variants appear to play a role in alcohol sensitivity and alcohol metabolism. Many alcohol-metabolizing variants were replicated across the studies reviewed, such as ALDH2*2, confirming prior results of its robust association with AUD. Future genetic research should use larger sample sizes and more diverse populations to improve gene identification and obtain more generalizable results.