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Young people who have inherited a genetic variation leading to increased feeling of dizziness from smoking their first cigarettes have a higher risk of becoming addictive smokers, a team of researchers led by Marissa Ehringer of the University of Colorado has found.

Though scientists worldwide have spent decades studying the receptors to which nicotine binds, Ehringer’s team has established a link between the genes that code for these receptors, dizziness, and lifelong nicotine addiction. The findings add depth and clarity to an emerging picture of genetic vulnerability to tobacco addiction.

“People who say they experience a lot of dizziness tend to be the ones who go on to become dependent” on tobacco, notes Ehringer, associate professor of integrative physiology and director of the Genetics of Substance Abuse Laboratory at CU’s Institute for Behavioral Genetics.

Marissa Ehringer, associate professor of integrative physiology and director of the Genetics of Substance Abuse Laboratory at CU’s Institute for Behavioral Genetics

Ehringer’s collaborative study with a team led by Dr. Laura Bierut, a professor of psychiatry at Washington University in St Louis, was published earlier this year in the American Journal of Medical Genetics. It included 789 smokers and 811 people who had smoked at least 100 cigarettes in their lifetimes but had not become dependent on nicotine.

The test subjects were asked if they experienced—and how intensely they experienced—any of eight feelings: pleasant sensations, unpleasant sensations, nausea, relaxation, dizziness, pleasurable rush or buzz, coughing or difficulty inhaling.

Those who recalled feeling extremely dizzy after smoking were more likely to harbor a specific genetic variation in a nicotinic receptor gene (CHRNA10).   “Nobody cared about alpha 10,” Ehringer recalls. Now that they’d found a link between a subjective experience and a new gene, the team was left with a question: “What the heck is alpha 10?”

She mentioned this to Michael Marks, an IBG researcher and international expert on the nicotinic receptor genes, who said the finding was interesting, because CHRNA10 genes are expressed in the inner ear. “Their location in the inner ear corresponds nicely with a possible involvement in mediating a ‘dizziness’ phenotype” (a trait traceable to genetics), Ehringer’s team writes.

Marks’ insight highlights IBG’s wide expertise and collaborative spirit, Ehringer notes. “How much fun is that, to be able to work with the people who are the experts?”

Ehringer acknowledges that a feeling of dizziness, which is unpleasant for many people, might seem a counter-intuitive harbinger of tobacco dependence. But those who are predisposed to an addiction might be attracted to such intense feelings, even if it the feelings seem out of control, she adds.

A prior study by Ehringer’s group, led by Joanna Zeiger and Brett Haberstick at the Institute for Behavioral Genetics, had established a link between another genetic variant in the CHRNB3 gene with dizziness and tobacco addiction. Along with prior studies, they help identify genes that contribute to nicotine addiction.

The work of Ehringer, Zeiger and other scientists employs new methods of associating subjective human experiences—such as dizziness—with specific genetic variants. She says being able to link people’s response to smoking with specific genes is the result of a new, “cool, analytical approach” that allows researchers to associate genes not only with what people do (smoke habitually) but also with how they feel (dizzy).

As Ehringer notes, one long-term aim of such research is to help identify those who are at higher risk of nicotine addition. “We have this hope that if you could tell someone, ‘You’re loaded; please don’t even try smoking,’ that that would go somewhere.”  But also understanding the genetics of addiction provides insight into the biology of addiction, which may lead to improved treatments.

Ehringer hopes that the study on dizziness and CHRNA10 is replicated. This study drew upon adults’ recollection of their initial smoking experiences. Studies of younger people, including studies of adolescents before they start smoking, are logical next steps.

The work of Ehringer’s team builds on an emerging body of evidence showing potential links between certain genes that code for different receptor proteins, (which impact nicotine’s attachment to the receptor) and a host of smoking behaviors, including addition addiction, age of first smoking, pleasure derived from first cigarettes, lung cancer and now dizziness. These genes are also implicated in alcohol dependence and chronic obstructive pulmonary disease.

As Ehringer notes, in most cases, about half of the factors contributing to human behaviors are believed to stem from multiple genetic factors and half from multiple environmental factors.

This means that genetic susceptibility to tobacco dependence does not doom people to addiction or disease. But it does indicate that those “loaded” with genetic predispositions are more likely to start smoking and have more trouble stopping.

Genetic research on tobacco dependence has blossomed in recent years.

In 2008, three groundbreaking articles appeared in the journals Nature and Nature Genetics. They reported that people with certain neuronal nicotinic receptor genes on chromosome 15 were more likely to become addicted to tobacco, more likely to smoke more cigarettes daily (thereby worsening the addiction), and more likely to develop lung cancer.

The scientists could not determine if the higher incidence of lung cancer were because of the genetic variation or because of the excessive smoking. “We still don’t know the answer to that,” Ehringer notes.

But researchers have amassed a rapidly increasing body of knowledge linking these genetic variants to tobacco addiction, responses and disease.

“It’s complicated,” Ehringer observes. “Unfortunately, that’s what makes behavior complicated. But the complexity is also what makes behavior unique and interesting.”

Tobacco use kills more than 5 million people annually and is a risk factor for six of the eight leading causes of death, according to the World Health Organization. Though tobacco use has declined in recent decades in the United States, about 20 percent of U.S. adults use the drug, reports the U.S. Centers for Disease Control and prevention.

Ehringer’s research is supported by the National Institutes of Health  (National Institute on Alcohol Abuse and Alcoholism and National Institute on Drug Abuse). This year, she was promoted to the rank of associate professor with tenure, and the Department of Integrative Physiology noted that it is “fortunate to claim a colleague of her caliber among our ranks.”