A new study has developed a new model for examining the genetic risk for nicotine dependence.
Tobacco smoking carries undeniable health risks, and being unable to quit or moderate smoking draws out the problem. While some people may be casual smokers and can easily quit, others become heavy smokers who struggle to quit. This risk for nicotine dependence comes from a complex mix of environmental, behavioural, and genetic factors.
Twins studies indicate that 40 to 70 percent of the risk factors are heritable. Until recently, however, studies have only explained about 1 percent 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 led by psychologists at Emory University leveraged genome-wide association studies for a range of different traits and disorders correlated with nicotine dependence and explained 3.6 percent of the variation in nicotine dependence. The findings were reported in the journal Nicotine & Tobacco Research.
Higher polygenetic scores for a risk for schizophrenia, depression, neuroticism, self-reported risk-taking, a high body mass index, alcohol use disorder, along with more cigarettes smoked a day were all indicators of a higher risk for nicotine dependence, the researchers found. Meanwhile, the results showed that polygenetic scores associated with higher education attainment lowered the risk for nicotine dependence.
Senior author Rohan Palmer, assistant professor, Behavioral Genetics of Addiction Laboratory, Emory University explained: “If you look at the joint effect of all of these characteristics, our model accounts for nearly 4 percent 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,”
“What we’re finding,” Prof Palmer added, “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.”
“All of the traits and diseases we looked at are polygenic, involving multiple genes,” added first author Victoria Risner, who did the work as an Emory undergraduate majoring in neuroscience and behavioural biology. “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,” Prof Palmer said.
Though smoking hazards are well known, about 14 percent of Americans use tobacco daily. Around half a million people die each year in the US from smoking or exposure to smoke, and another 16 million have serious illnesses caused by tobacco use, including cancer, cardiovascular disease, and pulmonary disease. While chemicals produced during smoking and vaping cause the health impacts, nicotine hooks people on these habits.
Risner worked on this paper for her Honours thesis. “Nicotine dependence was interesting to me because the vaping scene was just arriving while I was an undergraduate,” she 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.” Risner is now in medical school at University of North Carolina.
The work made use of genome-wide association studies for a range of traits and disorders. The researchers then sought matching variants in genetic data from a nationally representative sample of Americans with nicotine dependence. Polygenetic scores for the different traits and disorders either raised or lowered the risk for that dependence. The strongest predictors were number of cigarettes smoked per day, self-perceived risk-taking, and educational attainment.
The multi-variant, polygenetic model offers a path forward. For instance, a clearer picture of heritability for nicotine dependence, 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,” Prof Palmer said.
“Just a few decades ago, it was not well understood that nicotine dependence could have a genetic component,” Risner said. “Genetic studies may help reduce some of the stigma society has against substance use disorders, while also making treatment more accessible.”
Source: Emory Health Sciences
Journal information: Risner, V A., et al. (2021) Multi-Polygenic Analysis of Nicotine Dependence in Individuals of European Ancestry. Nicotine & Tobacco Research. doi.org/10.1093/ntr/ntab105.
