Alcoholism is a complex, genetically influenced disorder. Multiple phenotypes – measurable and/or observable traits or behavior – contribute to the risk of developing alcoholism, particularly disinhibition, alcohol metabolizing patterns, and a low level of response (LR) to alcohol.
A low LR to alcohol seems to be particularly relevant, with data indicating that LR relates to risk status, predicts future alcoholism, and has a heritability as high as 60 percent. A review in the October issue of Alcoholism: Clinical & Experimental Research examines previous research, seeking to identify those genes that may contribute to a low LR to alcohol.
"Prospective studies have shown that a low response to alcohol absolutely does increase your risk for future alcohol-related problems, at least in part by changing your expectations of what it is that you expect during drinking," said Marc A. Schuckit, director of the Alcohol Research Center, Veterans Affairs San Diego Healthcare System, professor of psychiatry at the University of California, San Diego, and first author of the study.
"However," Schuckit added, "the key is that people drink – especially early in their careers – for effect, which often means intoxication. An individual who experiences not much of an effect from alcohol will still feel effects like anybody else, but they'll just require more to do it, and this will probably impact their expectations of what alcohol is going to do for them."
"Different people have a different initial response to alcohol, also known as level of sensitivity," said David Goldman, chief of the Laboratory of Neurogenetics at the National Institute on Alcohol Abuse and Alcoholism. "Some people are a 'cheap date' or 'cheap drunk,' if you will, they're tipsy after only one drink versus others who can 'drink you under the table' and are still standing and not very affected even after several drinks."
Goldman noted that previous research has already taken step one, uncovering that a lower response to alcohol is predictive of future alcoholism. Step two, he said, was the discovery of the greater similarity in alcohol response between siblings or between parents and their offspring than you would expect from the random population, which directly implies there are genes that underlie that heritability. Step three, he added, is the current study that seeks to identify those genes.
Schuckit and his colleagues reviewed both animal and human English-language studies developed since January 1998, listed on Medline, and with appropriate keywords (n= 135). They then synthesized the studies' results, searching for potential patterns.
Reviewers identified several genes that may contribute to a low LR to alcohol, and thus, to an elevated risk for alcohol-use disorders. The genes of potential interest fall into several categories, including: second messenger systems, neurotransmitters or drug-related receptors, genes that affect alcohol metabolism, and genes that might relate to an overlap in the risk for alcoholism and some psychiatric conditions.