Given the genetic complexity of the disease, the search for alcoholism genes has been hindered by the tools geneticists have had at their disposal – only 10 or 15 years ago it was impossible to examine the expression of more than one gene at a time. In fact, Eric Nestler, chairman of psychiatry at the University of Texas Southwestern Medical Center in Dallas, who studies the genetics of addiction, says it’s been so difficult to find genes for alcoholism that “there’s been a bit of nihilism creeping into the field.”
But, Williams says, “We now have terrific tools,” such as increasingly cheaper, higher throughput DNA microarrays. “Looking for genes is getting faster.” The INIA study, he says, is an example of how quickly new models can be generated using these tools.
Because Bergeson’s group wasn’t looking at specific regions or for particular genes, the study had some unexpected results. One-quarter of the 3,800 candidate genes are of unknown function – the INIA group would have missed them with a narrower search.
We should “expect to be surprised” by the genes involved in complex diseases, says Nestler, because they “might not be obvious to us.” Indeed, of the 36 genes the INIA group poses as possible contributors to human alcoholism, says Williams, several are associated with non-neuronal brain cells, called glia, which researchers would not have guessed were involved with alcoholism.
Williams says broad approaches like Bergeson’s can illuminate surprising genes and help scientists avoid what he calls the “lamppost effect”: researchers studying addiction looking at the same group of genes and pathways – because that’s where the most illumination is.
Now the latest findings in mice need to be used to understand alcoholism in humans. The National Institute on Alcohol Abuse and Alcoholism, which funded the study, has a database of thousands of DNA samples from both alcoholics and their families. Bergeson says it would be relatively easy to bring this information together with her candidate genes from mice and look for commonalities.