Scientists have found that the genes which influence the amount of alcohol people drink may be distinct from those that affect the risk of alcoholism.
A large number of studies have focused on a genetic predisposition to alcoholism. They presume that the genes involved in this disorder, combined with environmental factors, influence susceptibility to alcohol dependence.
The various genetic pathways affecting alcohol drinking behavior have been investigated by Dr. Boris Tabakoff and his team at the University of Colorado-Denver using both rats and humans.
They compared genes involved in alcohol pathways in rats with human genes, using male study participants from Montreal, Canada and Sydney, Australia, to identify common genetic factors across species. Alcohol consumption among the participants ranged from abstinence to heavy intake, and drinking patterns were recorded.
The researchers discovered that drinking behavior is linked to the “pleasure and reward” pathways in the brain, and also to some of the systems that control food intake. In the journal BMC Biology, they write that the results emphasize the importance of looking at signaling pathways rather than single genes, and show cross-species similarities in predisposition to alcohol consumption.
“Our results also suggest that different genetic factors predispose to alcohol dependence versus alcohol consumption,” they add.
Dr. Tabakoff said, “We know that high levels of alcohol consumption can increase the risk of becoming alcohol dependent in those who have a genetic makeup that predisposes to dependence. This is a case of interaction between genes and environment.
“Indeed, in our study we found that higher alcohol consumption in humans was positively correlated with alcohol dependence. However, because different sets of genes seem to influence the level of alcohol consumption, as opposed to propensity for alcohol dependence, we are confronted with great variation in humans.”
He explains that people with genes that predispose them to drink only moderate amounts of alcohol may still have the genetic predisposition to lose control over their drinking behavior, and perhaps become alcohol dependent. On the other hand, those with a tendency to drink larger amounts of alcohol may not have the genes that predispose them to become dependent.
The reasons for differences in alcohol intake between people are the subject of an immense amount of research. Both environmental and genetic factors are thought to contribute, but there is often a lack of discrimination between alcohol consumption in dependent and nondependent individuals. There is no clear reason to assume that the same genetic factors are responsible. In fact, say the team, “one can interpret some of the data collected with mice to show a dissociation between a propensity for high alcohol consumption and propensity for physical dependence.”
They conclude, “The genetic factors that contribute to the full range of alcohol consumption versus alcohol dependence in humans are distinct.”
In 2008, experts from the National Institute on Alcohol Abuse and Alcoholism in Maryland carried out a review of the work done so far on genes and alcohol. Dr. Francesca Ducci and colleagues write, “Alcoholism is a chronic relapsing disorder with an enormous societal impact. Understanding the genetic basis of alcoholism is crucial to characterize individuals’ risk and to develop efficacious prevention and treatment strategies.”
They found that genetic factors account for 40 to 60 percent of the variance between people in risk of alcoholism. The genes involved in susceptibility to alcoholism include both alcohol-specific genes and those that affect neuronal pathways to do with reward, behavioral control and resilience to stress.
Major progress in gene identification has occurred in recent years, they write, but “the genetic determinants of alcoholism remain to be discovered.” Nevertheless, a technological revolution has occurred, allowing genome-wide searches. Genomes can now be assessed at a level of detail that was previously inconceivable, they explain, and new technologies and different approaches “promise to increase our understanding of the mechanisms by which genetic variation alters molecular function and predisposes individuals to alcoholism and other diseases.”
They experts conclude that, “Although the genetic bases of alcoholism remain largely unknown, there are reasons to think that more genes will be discovered in the future. Multiple and complementary approaches will be required to piece together the mosaic of causation.”
This work demonstrates the value of linking animal studies with genome-wide screening in humans to produce valuable findings on alcoholism and other drinking patterns.
Tabakoff, B. et al. Genetical genomic determinants of alcohol consumption in rats and humans. BMC Biology, published online October 27, 2009.
Tabakoff, B. et al. The genomic determinants of alcohol preference in mice. Mammalian Genome, Vol. 19, May 2008, pp, 352-65.
Ducci, F. and Goldman, D. Genetic approaches to addiction: genes and alcohol. Addiction, Vol. 103, September 2008, pp. 1414-28.