The Genetics of Nicotine Addiction

Researchers at the University of Iowa have identified certain genetic profiles that may be linked to a person’s risk for developing nicotine addiction and other psychological behaviors. Using a genome-wide scan, scientists analyzed blood samples from smokers versus nonsmokers and found similar genetic patterns among smokers that may one day be used as a genetic test to determine who may be more vulnerable to nicotine addiction.

 

“When you look at substance-abuse disorders and antisocial behavior, these are the last vestiges of the belief that mental impairments are related to moral will,” says Tracy Gunter, director of forensic psychiatry at the University of Iowa and a coauthor of the study. “And one of the exciting things in this work is [that] it’s beginning to form ideas that folks with these disorders are biologically different.”

In the past few years, researchers around the world have zeroed in on various genetic regions believed to be involved in one’s vulnerability to addiction. Some have studied genes that control certain neurotransmitters in the brain, while others have looked at genes related to addictive traits like risk taking and impulsivity. Gunter and her colleagues chose to look at the genome as a whole and observe which genes are turned on and which turned off in people with a long history of smoking.

“One gene itself doesn’t tell you whether you have a disorder,” says Robert Philibert, a University of Iowa professor of psychiatry and the study’s lead author. “But if you measure 30 or 40, you come up with a good risk. So what we do is spot the biology.”

In this latest study, published in the American Journal of Medical Genetics, Philibert and his colleagues analyzed the DNA samples of 94 people, some smokers and some nonsmokers. Using a technique called transcriptional profiling, they looked at all 30,000 genes of the human genome, fluorescently labeling those that were turned on versus those that were turned off in both groups. What they found was both promising and daunting: 579 genes were more activated and 584 other genes were less activated in smokers versus nonsmokers.

“This is sort of like shining a light in a tomb,” says Philibert. “It says there’s a lot here, but it doesn’t tell you anything about it. In order to really explore the biology, people will have to replicate this.”

Gunter adds that few psychological behaviors exist alone. For example, people who smoke may also have panic disorders or depression, each of which may involve a number of different genes. “How do you sort that out?” Gunter asks. “Is a genetic test disorder- specific, or specific to a cluster of disorders? There may be some sites that contribute more to prediction of a disorder than other sites. In the years to come, could we prune that down? Maybe.”

There’s also a question of whether, once a person starts smoking, increased nicotine consumption causes certain genes to turn on or off. To that end, Philibert plans to run similar genome-wide analyses on younger people who have not yet started smoking but may have a family history of nicotine dependence. He will also analyze DNA samples from patients with single psychological diagnoses to obtain what he calls a “cleaner phenotype.”

Anthony Hinrichs, assistant professor of psychiatry at Washington University, in St. Louis, studies genes that code for certain nicotine receptors in the brain. He sees this latest approach as casting a wide net for other potentially related genes.

“Transcriptional profiling in general, and this study in particular, are very promising ways of nominating candidate genes,” says Hinrichs. “I’m sure that these genes will now be on the map for other investigators.”

However, Hinrichs believes it will be a while before scientists can design accurate genetic tests for such disorders. “So far, researchers have identified a number of genetic markers which may increase susceptibility to drug addiction,” says Hinrichs. “Any of these would only increase the risk of addiction by a small percentage. We certainly have a long way to go before we can routinely use genetic tests.”

Meanwhile, Gunter and Philibert recognize that this kind of genetic testing comes with a host of ethical questions.

“There are some people [to whom] you may be able to say on a genetic basis, ‘You should never take the first drink,’” says Gunter. “And some will listen, and some may not. But it may have more impact on somebody if you are able to say, ‘This is why you, as an individual, don’t need to take the first drink: because you are at a particular risk for this to become a dependency, and this is how we know.’ That’s different from taking a profile and saying, ‘This is another alcoholic; I’m not going to insure them.’ Our part in this is to inform them of the level of their risk so it’s truly an informed choice.”