A new study uses genome-wide association studies for a range of different traits and disorders correlated with nicotine dependence and explains 3.6% of the variation in nicotine dependence.

In other words, the finding clarifies why some people casually smoke cigarettes for a while and then stop without a problem, while others develop long-term, several packs-per-day habits. A complex mix of environmental, behavioral, and genetic factors appear to raise this risk for nicotine dependence.

Studies of groups of twins suggest that 40-70% of the risk factors are heritable. Until recently, however, studies have only explained about 1% of the observed variation in liability to nicotine dependence, using a genetic score based on how many cigarettes a person smokes per day.

The new study offers a new model for examining this genetic risk. The journal Nicotine & Tobacco Research has published the finding.

Higher polygenetic scores for a risk for schizophrenia, depression, neuroticism, self-reported risk-taking, a high body mass index, alcohol use disorder, along with a higher number of cigarettes smoked per day were all indicators of a higher risk for nicotine dependence, the study finds. And polygenetic scores associated with higher education attainment lowered the risk for nicotine dependence, the results show.

“If you look at the joint effect of all of these characteristics, our model accounts for nearly 4% of the variation in nicotine dependence, or nearly four times as much as what we learn when relying solely on a genetic index for the number of cigarettes someone smokes daily,” says Rohan Palmer, senior author of the study and assistant professor in Emory University’s psychology department, where he heads the Behavioral Genetics of Addiction Laboratory.

“What we’re finding,” Palmer adds, “is that to better leverage genetic information, we need to go beyond individual human traits and disorders and think about how risk for different behaviors and traits are interrelated. This broader approach can give us a much better measure for whether someone is at risk for a mental disorder, such as nicotine dependence.”

Substance use disorders

Rohan Palmer leads the psychology department’s Behavioral Genetics of Addiction Laboratory that is developing new methods to better understand what makes people vulnerable to substance use disorders.

“All of the traits and diseases we looked at are polygenic, involving multiple genes,” adds Victoria Risner, first author of the study, who did the work as an Emory undergraduate. “That means that millions of genetic variants likely go into a complete picture for all of the heritable risks for nicotine dependence.”

The researchers hope that others will build on their multi-trait, polygenetic model and continue to boost the understanding of the risk for such complex disorders. “The more we learn, the closer we can get to one day having a genetic test that clinicians can use to inform their assessment of someone’s risk for nicotine dependence,” Palmer says.

Although the hazards of smoking are well established, about 14% of Americans report daily use of tobacco. Around 500,000 people die each year in the United States from smoking or exposure to smoke, and another 16 million live with serious illnesses caused by tobacco use, including cancer, cardiovascular disease, and pulmonary disease. While the toxic chemicals produced during smoking and vaping are what cause harmful health effects, it’s the addictive component of nicotine that hooks people on these habits.

“Nicotine dependence was interesting to me because the vaping scene was just arriving while I was an undergraduate,” Risner says. “I saw some of my own friends who were into vaping quickly becoming dependent on it, while some others who were using the same products didn’t. I was curious about the genetic underpinnings of this difference.”

Predicting nicotine dependence

The project leveraged genome-wide association studies for a range of traits and disorders. The researchers then looked for matching variants in genetic data from a national representative sample of Americans diagnosed with nicotine dependence. The results show how polygenetic scores for the different traits and disorders either raised or lowered the risk for that dependence. The number of cigarettes smoked per day, self-perceived risk-taking, and educational attainment were the most robust predictors.

The multi-variant, polygenetic model offers a road map for future studies. A clearer picture of heritability for nicotine dependence, for instance, may be gained by adding more risk associations to the model (such as nicotine metabolism) and clusters of polygenic traits (such as anxiety along with neuroticism).

“As we continue to zero in on who is most at risk for becoming nicotine dependent, and what inter-related factors, whether genetic or environmental, may raise their risk, that could help determine what intervention might work best for an individual,” Palmer says.

“Just a few decades ago, it was not well understood that nicotine dependence could have a genetic component,” Risner says. “Genetic studies may help reduce some of the stigma society has against substance use disorders, while also making treatment more accessible.”

Additional coauthors of the study are from Emory; the University of Helsinki; Brown University; the Providence VA Medical Center; the Jackson Laboratory in Bar Harbor, Maine; Purdue University; and the University of Colorado at Boulder.

Funding for the work came from the National Institute on Drug Abuse and the Academy of Finland.

Source: Emory University