Searching for most appropriate genetic factors that contribute to alcohol sensitivity

Alcohol use disorder (AUD) is a complex trait, both in its causes and characteristics. Individuals' sensitivity to alcohol can predict their risk of adverse alcohol outcomes like AUD. Further, AUD runs in families, reflecting in part a genetic component. Alcohol sensitivity includes multiple sub-types whose characteristics (phenotypes) reflect the genetic and environmental factors that interact to produce the disorder. This critical review examines phenotypes related to a person's response to alcohol, with an emphasis on specific gene variants that potentially impact alcohol sensitivity.

The existing literature points to a wide range of genetic mechanisms that could contribute to alcohol responses. This review offers the following insights:

  • There are many ways to study alcohol sensitivity, and no single approach is best for evaluating alcohol sensitivity. Although these methods have the benefit of describing multiple aspects of an alcohol response, they also highlight the complexities involved in choosing the most appropriate research approach.
  • There also appear to be a wide range of genetic variants that contribute to alcohol responses. Given the characteristics of most genetically complex traits and the range of alcohol-related brain effects, the most promising results have been for genes in the GABA, glutamate, opioid, dopamine, serotonin, and cholinergic neurotransmitter systems.
  • Future research on genes that contribute to how a person responds to alcohol should: 1) improve our understanding of how low responders and alcohol-related stimulation relate to future alcohol problems; 2) identify earlier the genes that contribute to alcohol sensitivity, potentially leading to interventions that might lessen vulnerability; and 3) help identify the biological underpinnings of AUDs, possibly those that may lead to new treatments.
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