Simplifying the Search for Genetic Risk in Alcohol Dependence

by Kayt Sukel

June 10, 2010

Epidemiological studies have long suggested that alcohol dependence is an inherited disorder. As genome-wide surveys became available over the past decade, scientists have hoped to find the gene (or genes) behind this relationship. An analysis by the researchers at the Virginia Commonwealth University School of Medicine published in the April 5 issue of Alcoholism: Clinical and Experimental Research suggests that simple measures of alcohol consumption may make that search a little easier.

The interplay of genetics and environment in alcohol dependence

Research in the epidemiological field suggests that at least half the incidence of alcoholism is inherited from the family line. But Ricardo Pautassi, a researcher at the Universidad Nacional de Córdoba in Argentina who studies alcohol abuse in teenagers, says it’s not clear what factors are in play in this inheritance.

“Basically that 50 percent is just this number yielded by the studies,” Pautassi says. “We simply don’t know how that number accounts for the different types of alcoholism or how genetic components may translate into a given mechanism for alcohol dependence.”

As genome-wide association studies have become more popular, a few “genes of interest” have come to light. These include some involved in the metabolization of alcohol as well as one linked to the development of receptors for the neurotransmitter gamma-aminobutyric acid (GABA). But because it’s unlikely there is a single smoking gun gene involved in alcohol dependence—and because environmental factors that have been associated with alcoholism like age of first drink, frequency of consumption and binge behaviors also muddy the waters—it is a challenge for researchers to understand the nature of a genetic predisposition to the disorder.

“We expect that genetic and environmental factors, on average, offer the same contribution to the disease. That’s true for most human diseases including cancer, diabetes, and high blood pressure,” says Laura Bierut, a researcher at Washington University in St. Louis. “The difficulty with the genetic aspects is there are likely to be many genes of small effect contributing instead of a single, clear gene responsible.”

Simplifying the search

Genome-wide association studies, especially when looking at genes of small effect, require extremely large sample sizes. Researchers interested in alcohol dependence have had difficulty finding data sets large enough to find significant results, mainly because diagnosis of alcohol dependence has, to date, required a lengthy diagnostic assessment. Kenneth Kendler and Danielle Dick, at the Virginia Commonwealth University School of Medicine, assessed data from a large twin registry to examine genetic factors related to alcohol dependence. They that by taking four simple measures of alcohol consumption during the time of life when a person was drinking heaviest—drinking frequency, regular quantity, maximum quantity, and drunk frequency—they could capture genetic risk for alcohol dependence as well as a psychiatric assessment.

“Essentially, this study tells us that you don’t need a full psychiatric interview to genetically index individuals at risk for alcohol dependence,” says Dick.

This finding is very similar to a study by Julia Grant and colleagues at Washington University in St. Louis, who tested the genetic overlap between alcohol dependence symptoms and consumption measures in a different twin set. They published their research in the Oct. 15, 2009, issue of Biological Psychiatry. 

“We looked at genetic overlap in much the same way Kendler and his colleagues did,” says Grant. “We found that the genetic overlap between consumption measures and alcohol dependence was very high.”

Next steps

Both findings are immediately useful for genetic research. Instead of collecting new data sets on alcoholism that include the full psychiatric assessment, researchers can examine existing data for other diseases that include questions about heaviest lifetime drinking (sets like, for example, diabetes).

“The fact that a few simple questions concerning consumption are highly overlapping with the more detailed measures when it comes to genetic risk is encouraging,” says Grant. “This gives us a quick way to get at genetic risk in a complex disease.”

And with a simplified search for potential risk genes, clinicians can better understand underlying biological pathways and use it to assist in developing new treatments.

“As we get a better handle on what the genetic factors are, we can see whether there are different biological predispositions for alcohol dependence,” says Dick. “And that may help us understand how to treat it.”