Researchers have identified 930 genes in rats linked to alcoholism, indicating that it is a highly complex disorder influenced by many genes and the environment.
Alcohol-craving rats provided researchers at Purdue University and Indiana University in the US with a detailed look into the complicated genetic underpinnings of alcoholism.
By comparing the genomes of rats that drank compulsively with those that abstained, researchers confirmed genes previously identified as being linked to alcoholism and uncovered new genes and neurological pathways, some of which could be promising targets for treatment.
However, the sheer number of genes that contribute to the trait suggests pharmaceutical treatments for alcoholism could be difficult to develop, said William Muir, professor at Purdue University.
"It's not one gene, one problem. This probably dashes water on the idea of treating alcoholism with a single pill," said Muir. One of the best predictors of alcoholism in humans is the drinking behaviour of their families.
However, 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. Separating out the influence of genetics on drinking habits from other factors such as stress, boredom or peers who drink is not possible in humans.
To gain insights into genes that contribute to alcoholism, researchers used a model based on rats, mammals with which we share a majority of genes. Beginning with a population of genetically diverse rats, researchers bred two lines: one group that displayed classic clinical signs of alcoholism and another that completely abstained from alcohol.
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.
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 highlighted 930 genes associated with excessive drinking behaviour.
While the researchers stressed that the genetic complexity of alcoholism complicates potential treatments, they found a signalling pathway which can control a sense of reward in the brain and may be a possible target for treatments due to the number of alcoholism-associated genes it contains.
The study was published in the journal PLOS Genetics....