More than 900 genes linked to alcoholism in rats

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A new study with rats suggests the genetic roots of alcoholism are incredibly complex. Researchers identified 930 genes associated with excessive drinking—on par with the number of genes involve in human height.

The sheer number of genes that contribute to alcoholism suggests pharmaceutical treatments could be difficult to develop, says William Muir, professor of genetics at Purdue University.

“We all have the genes for alcoholism, but our genetic abilities to control it differ.”

“It’s not one gene, one problem,” he says. “This trait is controlled by vast numbers of genes and networks. This probably dashes water on the idea of treating alcoholism with a single pill.”

One of the best predictors of alcoholism in humans is the drinking behavior of their families. But to what extent this link can be chalked up to inherited genetics—versus a shared environment – has been poorly understood and a challenge to study. Parsing out the influence of genetics on drinking habits from other factors such as stress, boredom, or peers who drink is not possible in humans.

“It’s very difficult to tease out the difference between what your genes are telling you to do and what you choose to do,” Muir says.

Breeding rats that like to drink

To gain insights into genes that contribute to alcoholism, Muir and Feng Zhou, a professor of neuroscience at Indiana University School of Medicine, used a model based on rats, mammals with which we share a majority of genes.

Beginning with a population of genetically diverse rats, researchers at the Indiana Alcohol Research Center bred two lines: one group that displayed classic clinical signs of alcoholism and another that completely abstained from alcohol.

Breeding rats to drink was no small challenge and required several decades, Muir says. Like most animals, rats tend to have a natural aversion to drinking a high concentration of alcohol.

These mutant worms can’t get drunk

“But typical of any genetic study, there’s always an outlier—in this case, a rat that will drink large amounts,” he says.

Choosing and breeding the rare rats that would take a tipple of pure grain alcohol eventually yielded a line of rats that compulsively drank to excess, preferred alcohol to water, drank to maintain intoxication, performed tasks to receive alcohol and showed signs of withdrawal if alcohol was absent.

Still, rats responded to intoxication in individualized ways, Zhou says.

“Under the influence of alcohol, some rats became docile and fell asleep in a corner while others became aggressive,” he says.

It’s not just the genes

The researchers sequenced and compared entire genomes from 10 rats in each line to determine genetic characteristics of drinking and abstaining. They also repeated the experiment with two additional lines of alcohol-seeking and teetotaler rats to discern which gene alterations were the result of natural selection and which were random genetic crosses.

The results, published in PLOS Genetics, highlight 930 genes associated with excessive drinking behavior, the vast majority of which are in genetic regulatory regions, not coding regions, as many researchers previously expected. Muir compared coding regions to a car and regulatory regions to the gas and brake pedals that determine the car’s speed.

“We all have the genes for alcoholism, but our genetic abilities to control it differ,” he says.

While the researchers stressed that the genetic complexity of alcoholism complicates potential treatments, they pinpointed the glutamate receptor signaling pathway—which can control a sense of reward in the brain—might be a possible target for treatments due to the number of alcoholism-associated genes it contains.

Bigger buzz spells trouble for binge drinkers

One of the next steps in the research is to verify that the genes identified in alcoholic rats are relevant to human alcoholism.

Though the study shows there is a large genetic component to alcoholism, environment still plays a crucial role in shaping people’s drinking habits, the researchers says.

“Even with the same genetics, one person might be prone to getting drunk while another doesn’t drink at all,” Zhou says. “Your environment can trigger the expression of genetic tendencies toward alcoholism.”

Or, as Muir put it, “You can’t just blame your drinking on your parents.”

The National Institute on Alcohol Abuse and Alcoholism and the Indiana Alcohol Research Center funded the study.

Source: Purdue University